Levels Of Mutagenicity Research Articles

Response of Soybean Genotypes to Different Levels of Mutagens for Yield Related Attributes

Soybean (Glycine max L.) has a significant nutritional value. It comprises around 40% protein and 20% oil content. Soybean protein has valuable amino acid lysine (5%)...

Exposure to disinfection by-products in swimming pools and biomarkers of genotoxicity and respiratory damage – The PISCINA2 Study

BackgroundSwimming in pools is a healthy activity that entails exposure to disinfection by-products (DBPs), some of which are irritant and genotoxic. ObjectivesWe evaluated exposure to DBPs during swimming in a chlorinated pool and the association with short-term changes in genotoxicity and lung epithelium permeability biomarkers. MethodsNon-smoker adults (N = 116) swimming 40 min in an indoor pool were included. We measured a range of biomarkers before and at different times after swimming: trihalomethanes (THMs) in exhaled breath (5 min), trichloroacetic acid (TCAA) in urine (30 min), micronuclei in lymphocytes (1 h), serum club cell protein (CC16) (1 h), urine mutagenicity (2 h) and micronuclei in reticulocytes (4 days in a subset, N = 19). Several DBPs in water and trichloramine in air were measured, and physical activity was extensively assessed. We estimated interactions with polymorphisms in genes related to DBP metabolism. ResultsMedian level of chloroform, brominated and total THMs in water was 37.3, 9.5 and 48.5, μg/L, respectively, and trichloramine in air was 472.6 μg/m3. Median exhaled chloroform, brominated and total THMs increased after swimming by 10.9, 2.6 and 13.4, μg/m3, respectively. Creatinine-adjusted urinary TCAA increased by 3.1 μmol/mol. Micronuclei in lymphocytes and reticulocytes, urine mutagenicity and serum CC16 levels remained unchanged after swimming. Spearman correlation coefficients showed no association between DBP exposure and micronuclei in lymphocytes, urine mutagenicity and CC16. Moderate associations were observed for micronuclei in reticulocytes and DBP exposure. ConclusionsThe unchanged levels of the short-term effect biomarkers after swimming and null associations with personal estimates of exposure to DBPs suggest no measurable effect on genotoxicity in lymphocytes, urine mutagenicity and lung epithelium permeability at the observed exposure levels. The moderate associations with micronuclei in reticulocytes require cautious interpretation given the reduced sample size.

Impact of anthropogenic activities on mussel (Mytella guyanensis) in the Gulf of Paria, Trinidad

This body of work demonstrated the levels of selected contaminants (as well as their potential sources), in mussels (Mytella guyanensis) - a known bio-indicator of pollution, along the west coast (Gulf-of-Paria) of Trinidad. The findings demonstrated that polyaromatic hydrocarbons levels in the mussels investigated were moderate to high (201.80–1200.08 μg/kg). Notably, benzo(a)pyrene levels (1.15–9.32 μg/kg) exceeded the European Union guidelines at various sites. The distribution of PAHs and trace elements in the Gulf of Paria are impacted by tidal currents and local source discharge. Significant risks were identified from toxic carcinogenic equivalent levels (3.01 to 22.37 μg/kg) and mutagenic equivalent levels (3.98 to 38.61 μg/kg). The concentration of trace elements, Zn (46.05–56.36 mg/kg) and Cd (0.46–1.17 mg/kg), exceeded both local and international guidelines at certain sites investigated. The analysis revealed a high bioavailability of the identified pollutants in the Gulf of Paria from industrial, urban and marine activities.

Soil mutagenic activity in hazardous waste site of Kalush City (Western Ukraine)

<p>Frequency and spectrum of cytogenetic disorders in the cells of root meristem sprouts of <em>Triticum aestivum L.,</em> induced by soil contamination with hexachlorobenzene in the territory of toxic waste ground and Dombrovskyi potassium ore mine (Kalush city, Ivano-Frankivsk oblast), were studied. The concentration of hexachlorobenzene exceeded MPC (maximum permissible concentration) by 1233.3–18350 times. It has been established that chemical soil contamination causes the increase of the frequency of cytogenetic aberrations by 1.8-3.8 times. Its highest indicators were found under the most intensive soil contamination with hexachlorobenzene in the areas of toxic waste ground which were not recultivated. Frequency of cytogenetic disorders exceeded the control level by 3.4-3.8 times. The maintenance of high mutagenic activity of hexachlorobenzene remains in the soil of the recultivated area of the ground is confirmed by statistically reliable increase of the number of aberrant cells by 2.6-3 times. It has been shown that soil contamination of Dombrovskyi mine with the complex of natural-mineral compounds of mining-chemical raw materials causes the increase of mutagenic activity level of low concentrations of chemical gene-toxic factors of techno-genic origin, which is seen in the induction of higher level of cytogenic disorders compared with spontaneous indicators by 1.8-2.4 times. Spectrum of chromosome aberrations, which mostly included acentric fragments, expanded due to induced bridges, ring chromosomes and micronuclei. The share increase of the cells with dicentrics, caused by the effect of soil contamination with hexachlorobenzene in the territory of toxic waste ground, confirms the radiomimetic effect, resulted from the effect of chemical mutagen in high concentrations. Chemical pollutants of the soil of all the studied areas show the ability to cause mitosis disorder, connected with the damage of mitotic apparatus. A significant increase of disorder frequency of chromosome segregation can be the result of the interaction of mutagens not only with microtube proteins of division spindle but also with heterochromatin of near-center areas of chromosomes, which is typical for the mechanism of the emergence of cytogenetic aberrations under the effect of chemical supermutagens in high concentrations. The increase of the cell number with multiple aberrations under the effect of soil contamination with hexachlorobenzene in different concentrations proves high gene-toxicity of the chemical compound and the threat of severe genetic outcomes when it gets into the environment.</p>

Elevated Exposures to Polycyclic Aromatic Hydrocarbons and Other Organic Mutagens in Ottawa Firefighters Participating in Emergency, On-Shift Fire Suppression.

Occupational exposures to combustion emissions were examined in Ottawa Fire Service (OFS) firefighters. Paired urine and dermal wipe samples (i.e., pre- and post-event) as well as personal air samples and fire event questionnaires were collected from 27 male OFS firefighters. A total of 18 OFS office workers were used as additional controls. Exposures to polycyclic aromatic hydrocarbons (PAHs) and other organic mutagens were assessed by quantification of urinary PAH metabolite levels, levels of PAHs in dermal wipes and personal air samples, and urinary mutagenicity using the Salmonella mutagenicity assay (Ames test). Urinary Clara Cell 16 (CC16) and 15-isoprostane F2t (8-iso-PGF2α) levels were used to assess lung injury and overall oxidative stress, respectively. The results showed significant 2.9- to 5.3-fold increases in average post-event levels of urinary PAH metabolites, depending on the PAH metabolite (p < 0.0001). Average post-event levels of urinary mutagenicity showed a significant, event-related 4.3-fold increase (p < 0.0001). Urinary CC16 and 8-iso-PGF2α did not increase. PAH concentrations in personal air and on skin accounted for 54% of the variation in fold changes of urinary PAH metabolites (p < 0.002). The results indicate that emergency, on-shift fire suppression is associated with significantly elevated exposures to combustion emissions.

Effects of humic acids from landfill leachate on plants: An integrated approach using chemical, biochemical and cytogenetic analysis

Biological process treatment of landfill leachate produces a significant amount of sludge, characterized by high levels of organic matter from which humic acids are known to activate several enzymes of energy metabolism, stimulating plant growth. This study aimed to characterize humic acids extracted from landfill sludge and assess the effects on plants exposed to different concentrations (0.5, 1, 2 and 4 mM C L−1) by chemical and biological analysis, to elucidate the influence of such organic material and minimize potential risks of using sludge in natura. Landfill humic acids showed high carbon and nitrogen levels, which may represent an important source of nutrients for plants. Biochemical analysis demonstrated an increase of enzyme activity, especially H+-ATPase in 2 mM C L−1 landfill humic acid. Additionally, cytogenetic alterations were observed in meristematic and F1 cells, through nuclear abnormalities and micronuclei. Multivariate statistical analysis provided integration of physical, chemical and biological data. Despite all the nutritional benefits of humic acids and their activation of plant antioxidant systems, the observed biological effects showed concerning levels of mutagenicity.

Quantifying the contribution of dyes to the mutagenicity of waters under the influence of textile activities

The combination of chemical analyses and bioassays allows the identification of potentially mutagenic compounds in different types of samples. Dyes can be considered as emergent contaminants and were detected in waters, under the influence of textile activities. The objective of this study was to evaluate the contribution of 9 azo dyes to the mutagenicity of representative environmental samples. Samples were collected along one year in the largest conglomerate of textile industries of Brazil. We analyzed water samples from an important water body, Piracicaba River, upstream and downstream two main discharges, the effluent of a wastewater treatment plant (WWTP) and the tributary Quilombo River, which receives untreated effluent from local industries. Samples were analyzed using a LC-MS/MS and tested for mutagenicity in the Salmonella/microsome microsuspension assay with TA98 and YG1041. Six dyes were detected in the collected samples, Disperse Blue 291, Disperse Blue 373, Disperse Orange 30, Disperse Red 1, Disperse Violet 93, and Disperse Yellow 3. The most sensitive condition for the detection of the mutagenicity was the strain YG1041 with S9. The concentration of dyes and mutagenicity levels varied along time and the dry season represented the worst condition. Disperse Blue 373 and Disperse Violet 93 were the major contributors to the mutagenicity. We conclude that dyes are contributing for the mutagenicity of Piracicaba River water; and both discharges, WWTP effluent and Quilombo River, increase the mutagenicity of Piracicaba River waters in about 10-fold. The combination of chemical analysis and bioassays were key in the identification the main drivers of the water mutagenicity and allows the selection of priority compounds to be included in monitoring programs as well for the enforcing actions required to protect the water quality for multiple uses.

Mutagenicity and Phthalate Level of Bottled Water Under Different Storage Conditions

Mutagenicity and phthalate level of bottled water are still under-investigated. Five brands of still or carbonated mineral water bottled in PET, glass, or polycarbonate bottles were kept in sunlight or darkness at ambient temperatures or 37 °C for 0, 1, or 4 months. The ultraviolet (UV)-filtering capacity of bottles was also assessed. Concentrated organic fractions were analysed using the Ames test. Diisobutylphthalate (DIBP), diethylhexylphtalate (DEHP), and dibutylphthalate (DBP) were quantified by gas chromatography. Mean values of UVA and UVB reduction by bottle walls were 17 and 70% in PET, 16 and 70% in glass, and 66 and 86% in polycarbonate, respectively. Salmonella TA100 strain proved to be more sensitive than TA98 in the Ames test, and according to the test, we isolated direct-acting mutagens. The most mutagenic samples were identified after 1 month, stored at 37 °C and in sunlight. Water stored in bisphenol A-free polycarbonate was non-mutagenic. Phthalate concentrations were low initially and then ranged between <0.026–0.16 μg/L (DIBP), <0.29–11.72 μg/L (DEHP), and <0.005–0.2 μg/L (DBP); levels were the highest also after 1 month of storage. The highest mutagenicity and phthalate levels were detected similarly after 1 month of storage in mineral water, but mainly in different samples, and we found no significant correlation between them. Levels of phthalates were independent of bottle material. To sum up, natural organics in water can be important sources of mutagenic compound and phthalate formation. However, further analytical measurements should be performed to identify and follow-up the presence of genotoxic compounds in bottled mineral waters.

Presence of Aflatoxins (Mutagens and Carcinogens) in Industrialized Chili Sauces

Aflatoxins (AFs) are the most frequent mutagens, teratogens and carcinogens detected in food, and they are also present in all types of chili peppers and sauces made with them. Fifty-two different industrialized chili pepper sauces from markets in Mexico were analyzed for the presence of aflatoxins (AFB1, AFB2, AFG1 and AFG2). The chemical AF extraction and high performance liquid chromatography methods were validated based on the following parameters: selectivity, linearity (calibration curves), recovery percentages, limits of detection (LOD) and quantification (LOQ). The square of correlation coefficients (R2) were AFB1: 0.9973; AFB2: 0.9892; AFG: 0.9969; and AFG2: 0.9986. All curves were correct, with an average regression coefficient of R2 > 0.9892. The percentage of recovery, was 83% for AFB1 , 75% for AFB2, 96% for AFG1, and 81% for AFG2. The Limits of Detection (LOD) were 0.1 ng for AFB1, 0.01 ng for AFB2, 0.01 ng for AFG1, and 0.5 ng for AFG2. For the statistical analysis, the different chili sauce groups were analyzed and compared using a Kruskal-Wallis test, and the results showed no statistically significant differences among the samples with respect to the total aflatoxins (AFt) amounts. The removal of all high mutagenic levels of AFG1 (> 10 ppb) from the analysis did not change the results. Eight chili pepper sauces (15%) from the different groups surpassed the 10 ppb AFt tolerance limit of the Codex Alimentarius and had 15 to 116 μg kg-1 AFt. The average AFt from the 52 samples was 3.69 μg kg-1, which were all within the globally accepted limits. Thus, these results suggest that there is no consistent basis for warning the public about AFs in the most commonly used salsas, but their use should be moderated because many are not safe to eat.

Long-range transport of mutagens and other air pollutants from mainland East Asia to western Japan.

IntroductionAsian dust events, transport of dust particles from arid and semi-arid areas in China and Mongolia to the east by prevailing westerlies, are often observed in Japan in spring. In recent decades, consumption of fossil fuels has markedly increased in mainland East Asia with rapid economic growth, and severe air pollution has occurred. A part of air pollutants including mutagens, such as polycyclic aromatic hydrocarbons (PAHs), generated in mainland East Asia are thought to be transported to Japan by the prevailing westerlies, like Asian dust, and winter monsoon. The objective of this study was to clarify the long-range transport of mutagens and other air pollutants in East Asia. Thus, we collected total suspended particles (TSP) at a rural town in western Japan, namely, Yurihama in Tottori Prefecture, for 1 year (June 2012–May 2013), and investigated their chemical constituents and mutagenicity.ResultsMany TSP collected from January to March showed high mutagenicity toward Salmonella typhimurium YG1024 with and without S9 mix, and high levels of lead (Pb) and sulfate ions (SO42−), which are indicators of transboundary air pollutions from mainland East Asia, were detected in those TSP. A large amount of iron, which is an indicator of sand, was found in highly mutagenic TSP collected in March, but not in TSP collected in January and February. High levels of PAHs were detected in highly mutagenic TSP collected from January to March. The ratios of the concentration of fluoranthene to those of fluoranthene and pyrene suggested that the main source of PAHs in TSP collected in winter and spring was coal and biomass combustion. Backward trajectories of air masses on days when high levels of mutagenicity were found indicated that these air masses had traveled from eastern or northern China to Yurihama.ConclusionsThese results suggest that high levels of mutagens were transported from mainland East Asia to western Japan, and this transportation accompanied Asian dust in March, but not in January and February.

Seasonal Fluctuations in Air Pollution in Dazaifu, Japan, and Effect of Long-Range Transport from Mainland East Asia.

To clarify the seasonal fluctuations in air pollution and the effect of long-range transport, we collected airborne particles (n=118) at Dazaifu in Fukuoka, Japan, from June 2012 to May 2013 and measured Pb and SO4(2-), which are indicators of the long-range transport of anthropogenic air pollutants, as well as their mutagenicity, and other factors. The levels of airborne particles, Pb, and SO4(2-) were very high on March 4, 8, 9, and 19, and May 13, 21, and 22, 2013. The backward trajectories indicated that air masses had arrived from the Gobi Desert and northern China on those days. The mutagenicity of airborne particles was examined using the Ames test on Salmonella typhimurium YG1024. Highly mutagenic airborne particles were mostly collected in winter, and most of them showed high activity both with and without S9 mix. High levels of polycyclic aromatic hydrocarbons (PAHs) were found in many samples that showed high mutagenicity. For the samples collected on January 30, February 21, and March 4, the levels of Pb, SO4(2-), PAHs, and mutagenicity were high, and the backward trajectories indicated that air masses present on those days had passed through northern or central China. The Japan Meteorological Agency registered Asian dust events at Fukuoka on March 8, 9, and 19, 2013. The results of the present study suggest that high levels of anthropogenic air pollutants were transported with Asian dust. Similarly, long-range transport of air pollutants including mutagens occurred on days when Asian dust events were not registered.

Polycyclic aromatic hydrocarbons in settled dust particles in selected Ghanaian environments: Levels, source characterization, and assessment of inhalational health risks

Deposited total particulate matter samples were collected from 10 indoor sites within the Cape Coast and Komenda Edina Eguafo Abrem Municipalities of Ghana and analysed for polycyclic aromatic hydrocarbons (PAHs) using a Varian Gas Chromatography/Mass Spectrometry (GC/MS) system with 8400 auto-sampler. Quality control analysis using National Institute of Standards and Technology Standard Reference Material 1941B gave the PAH recoveries of 80.5% or better. The concentrations of the various individual PAHs in the particulate matter ranged from below detection limits to 3240 µg/kg. The results compared well with a similar study carried out in Palermo, Italy, which had concentrations between 0.01 and 25838.0 µg/kg. Assessment of their sources showed the emission of PAHs was from both combustion and petroleum sources. The cancer risk level for the various sites ranged between 2.6 × 10–7 and 3.6 × 10–4 with the upper limit being higher than the acceptable level of 10–5. The mutagenic risk levels of the PAHs in the air particulate matter collected from various sites also ranged from 2.0 × 10−6 to 3.3 × 10−4, showing certain levels of health risks. This study suggests that indoor air pollution, which has been relegated in most developing countries, should be taken seriously.

A novel antifungal is active against Candida albicans biofilms and inhibits mutagenic acetaldehyde production in vitro.

The ability of C. albicans to form biofilms is a major virulence factor and a challenge for management. This is evident in biofilm-associated chronic oral-oesophageal candidosis, which has been shown to be potentially carcinogenic in vivo. We have previously shown that most Candida spp. can produce significant levels of mutagenic acetaldehyde (ACH). ACH is also an important mediator of candidal biofilm formation. We have also reported that D,L-2-hydroxyisocaproic acid (HICA) significantly inhibits planktonic growth of C. albicans. The aim of the present study was to investigate the effect of HICA on C. albicans biofilm formation and ACH production in vitro. Inhibition of biofilm formation by HICA, analogous control compounds or caspofungin was measured using XTT to measure biofilm metabolic activity and PicoGreen as a marker of biomass. Biofilms were visualised by scanning electron microscopy (SEM). ACH levels were measured by gas chromatography. Transcriptional changes in the genes involved in ACH metabolism were measured using RT-qPCR. The mean metabolic activity and biomass of all pre-grown (4, 24, 48 h) biofilms were significantly reduced after exposure to HICA (p<0.05) with the largest reductions seen at acidic pH. Caspofungin was mainly active against biofilms pre-grown for 4 h at neutral pH. Mutagenic levels (>40 μM) of ACH were detected in 24 and 48 h biofilms at both pHs. Interestingly, no ACH production was detected from D-glucose in the presence of HICA at acidic pH (p<0.05). Expression of genes responsible for ACH catabolism was up-regulated by HICA but down-regulated by caspofungin. SEM showed aberrant hyphae and collapsed hyphal structures during incubation with HICA at acidic pH. We conclude that HICA has potential as an antifungal agent with ability to inhibit C. albicans cell growth and biofilm formation. HICA also significantly reduces the mutagenic potential of C. albicans biofilms, which may be important when treating bacterial-fungal biofilm infections.

A novel antifungal is active against Candida albicans biofilms and inhibits mutagenic acetaldehyde production in vitro.

The ability of C. albicans to form biofilms is a major virulence factor and a challenge for management. This is evident in biofilm-associated chronic oral-oesophageal candidosis, which has been shown to be potentially carcinogenic in vivo. We have previously shown that most Candida spp. can produce significant levels of mutagenic acetaldehyde (ACH). ACH is also an important mediator of candidal biofilm formation. We have also reported that D,L-2-hydroxyisocaproic acid (HICA) significantly inhibits planktonic growth of C. albicans. The aim of the present study was to investigate the effect of HICA on C. albicans biofilm formation and ACH production in vitro. Inhibition of biofilm formation by HICA, analogous control compounds or caspofungin was measured using XTT to measure biofilm metabolic activity and PicoGreen as a marker of biomass. Biofilms were visualised by scanning electron microscopy (SEM). ACH levels were measured by gas chromatography. Transcriptional changes in the genes involved in ACH metabolism were measured using RT-qPCR. The mean metabolic activity and biomass of all pre-grown (4, 24, 48 h) biofilms were significantly reduced after exposure to HICA (p<0.05) with the largest reductions seen at acidic pH. Caspofungin was mainly active against biofilms pre-grown for 4 h at neutral pH. Mutagenic levels (>40 µM) of ACH were detected in 24 and 48 h biofilms at both pHs. Interestingly, no ACH production was detected from D-glucose in the presence of HICA at acidic pH (p<0.05). Expression of genes responsible for ACH catabolism was up-regulated by HICA but down-regulated by caspofungin. SEM showed aberrant hyphae and collapsed hyphal structures during incubation with HICA at acidic pH. We conclude that HICA has potential as an antifungal agent with ability to inhibit C. albicans cell growth and biofilm formation. HICA also significantly reduces the mutagenic potential of C. albicans biofilms, which may be important when treating bacterial-fungal biofilm infections.

Glutathione-dependent and -independent oxidative stress-control mechanisms distinguish normal human mammary epithelial cell subsets.

Mechanisms that control the levels and activities of reactive oxygen species (ROS) in normal human mammary cells are poorly understood. We show that purified normal human basal mammary epithelial cells maintain low levels of ROS primarily by a glutathione-dependent but inefficient antioxidant mechanism that uses mitochondrial glutathione peroxidase 2. In contrast, the matching purified luminal progenitor cells contain higher levels of ROS, multiple glutathione-independent antioxidants and oxidative nucleotide damage-controlling proteins and consume O2 at a higher rate. The luminal progenitor cells are more resistant to glutathione depletion than the basal cells, including those with in vivo and in vitro proliferation and differentiation activity. The luminal progenitors also are more resistant to H2O2 or ionizing radiation. Importantly, even freshly isolated "steady-state" normal luminal progenitors show elevated levels of unrepaired oxidative DNA damage. Distinct ROS control mechanisms operating in different subsets of normal human mammary cells could have differentiation state-specific functions and long-term consequences.

Hypotensive effect and endothelium-dependent vascular action of leaves of Alpinia purpurata (Vieill) K. Schum

The aims of this study were to evaluate the chemical profile, vascular reactivity, and acute hypotensive effect (AHE) of the ethanolic extract of leaves of Alpinia purpurata (Vieill) K. Schum (EEAP). Its chemical profile was evaluated using HPLC-UV, ICP-OES, and colorimetric quantification of total flavonoids and polyphenols. The vascular reactivity of the extract was determined using the mesenteric bed isolated from WKY. AHE dose-response curves were obtained for both EEAP and inorganic material isolated from AP (IAP) in WKY and SHR animals. Cytotoxic and mutagenic safety levels were determined by the micronucleus test. Rutin-like flavonoids were quantified in the EEAP (1.8 ± 0.03%), and the total flavonoid and polyphenol ratios were 4.1 ± 1.8% and 5.1 ± 0.3%, respectively. We observed that the vasodilation action of EEAP was partially mediated by nitric oxide (·NO). The IAP showed the presence of calcium (137.76 ± 4.08 μg mg-1). The EEAP and IAP showed an AHE in WKY and SHR animals. EEAP did not have cytotoxic effects or cause chromosomic alterations. The AHE shown by EEAP could result from its endothelium-dependent vascular action. Rutin-like flavonoids, among other polyphenols, could contribute to these biological activities, and the calcium present in EEAP could act in a synergistic way.

Chernobyl-Touched Children: E and A Hypovitaminoses-Related Mechanisms and Prevention of Radiogenic Mutagenicity and Teratogenicity

Children and their mothers affected by the Chernobyl catastrophy suffer with toxic lipoperoxic stress coupled with hypovitaminoses A and E. The relation of these primary biochemical disturbances to notorious somatic consequences on mutagenic and teratogenic levels caused by chronic low-dose radiation of children from radiopolluted regions had been investigated. Rational approaches to prevent or to treat indicated pathologies were developed either. Vitamins A and E blood levels for newborns from radio polluted regions were near a third of normal ones. Simultaneous increasing of lipo-peroxidation for studied children had tendency to correlate with their body stigmation. Radiogenic indices of mutagenicity and teratogenicity showed dramatic increases along with fall of the essential antioxidants. The peroral poly vitamin therapy of women at the beginning of 1st trimester pregnancy prevented or corrected evaluated abnormalities for their newborns. Vitamin-protected children had normal ranges for studied indices. The combination of radiogenic biochemical deviations is supposed to be the primary molecular mechanisms for children restorable somatic hyper mutations and irreversible body stigmations but preventable by essential antioxidants via their mothers at early pregnancy.

ALDH2 Genotype Has No Effect on Salivary Acetaldehyde without the Presence of Ethanol in the Systemic Circulation

BackgroundAcetaldehyde associated with alcoholic beverages was recently classified as carcinogenic (Group 1) to humans based on uniform epidemiological and biochemical evidence. ALDH2 (aldehyde dehydrogenase 2) deficient alcohol consumers are exposed to high concentrations of salivary acetaldehyde and have an increased risk of upper digestive tract cancer. However, this interaction is not seen among ALDH2 deficient non-drinkers or rare drinkers, regardless of their smoking status or consumption of edibles containing ethanol or acetaldehyde. Therefore, the aim of this study was to examine the effect of the ALDH2 genotype on the exposure to locally formed acetaldehyde via the saliva without ethanol ingestion.MethodsThe ALDH2 genotypes of 17 subjects were determined by PCR-RFLP. The subjects rinsed out their mouths with 5 ml of 40 vol% alcohol for 5 seconds. Salivary ethanol and acetaldehyde levels were measured by gas chromatography.ResultsAcetaldehyde reached mutagenic levels rapidly and the exposure continued for up to 20 minutes. The mean salivary acetaldehyde concentrations did not differ between ALDH2 genotypes.ConclusionsFor ALDH2 deficient subjects, an elevated exposure to endogenously formed acetaldehyde requires the presence of ethanol in the systemic circulation.ImpactOur findings provide a logical explanation for how there is an increased incidence of upper digestive tract cancers among ALDH2 deficient alcohol drinkers, but not among those ALDH2 deficient subjects who are locally exposed to acetaldehyde without bloodborne ethanol being delivered to the saliva. Thus, ALDH2 deficient alcohol drinkers provide a human model for increased local exposure to acetaldehyde derived from the salivary glands.

Influence of genetic polymorphisms on biomarkers of exposure and effects in children living in Upper Silesia

This article is a follow-up to our previous molecular epidemiology studies on the DNA damage in children from the Upper Silesia region of Poland. It is expected that metabolic and DNA repair gene polymorphisms may modulate individual susceptibility to environmental exposure. In this study, we investigate the association between polymorphisms of metabolising (CYP2D, EPHX1, GSTM1, GSTP1, GSTT1, NAT2) and DNA repair (XPD, XRCC1, XRCC3) genes and selected biomarkers of exposure and effect such as levels of 1-hydroxypyrene (1-OHP) and urinary mutagenicity, aromatic DNA adducts, sister chromatid exchange (SCE) and micronuclei (MN) in 74 children. Both 1-OHP concentration and urinary mutagenicity tested by TA98+S9 were significantly higher in individuals with EPHX1 (exon 4) Arg/Arg genotype than in individuals with other genotype. The EPHX1 (exon 3) significantly affected urinary mutagenicity tested with strain YG1024+S9. The urinary mutagenicity in individuals with Tyr/Tyr homozygotes was lower than in individuals with Tyr/His and His/His (1057±685 vs. 1432±1003 revertants/mol creatinine). XRCC3 Met/Met genotype was associated with significantly higher levels of 1-OHP in urine compared with only The/Met genotype. The PAH-DNA adduct levels in the subgroup with GSTM1 null genotype was 2-fold higher than in individuals with GSTM1 active (7.06±5.12 vs. 13.14±9.81 adduct/10(8) nucleotides). The mean level of aromatic DNA adducts in children with deletion of the GSTT1 gene was significantly higher compared with individuals with that gene present (8.03±6.23 vs. 14.66±10.70 adduct/10(8) nucleotides). Also the carriers of the XPD Lys/Lys genotype showed higher levels of DNA adducts than heterozygotes (13.16±9.70 vs. 6.81±5.86 adducts/10(8) nucleotides). Children carrying the XRCC3-241 Met/Met genotype exhibited a higher number of SCE in peripheral blood lymphocytes than carriers of Thr/Met allele (8.15±0.86 vs. 7.62±0.79 SCE/cell). It was also observed that children with the GSTP1 slow conjugator had significantly elevated MN in peripheral blood lymphocytes compared with fast conjugator (4.23±3.49 vs. 6.56±5.00 MN/1000 cells).

Evaluation of cytotoxic, mutagenic and antimutagenic potential of leaf extracts of three medicinal plants using Allium cepa chromosome assay

In the present study, the Allium cepa chromosome assay was employed as a preliminary test to investigate the mutagenic and antimutagenic potential of three plants, namely Clinacanthus nutans, Adhatoda vasica, and Carica papaya, used by traditional practitioners in Malaysia against a direct acting mutagen-Methyl Methanesulphonate (MMS). Onions were planted in various treatment groups: plant extract alone, treatment 1 (pre-treatment with MMS and transfer into plant extracts), and treatment 2 (mixture of MMS and plant extracts). The bulbs planted in the extract alone for cytotoxicity and mutagenicity assessment revealed that none of the extracts of the three plants except the 50 mg/kg of methanol extract of A. vasicawere cytotoxic to A. cepa cells, but a moderate level of mutagenicity was observed at 200 and 400 mg/kg of methanol extract of C. papaya and at 400 mg/kg of aqueous extract of C. nutans. Antimutagenic screening on the other hand revealed that all the extracts tested were able to reduce the percentage chromosomal aberration induced by MMS, both in treatment 1 and 2. Besides that, MMS-induced cell death was also observed to be reduced in onion root cells treated with the plant extracts. Therefore, taking all the results obtained into consideration, the order of the plant extracts with increasing suppressiveness against MMS was C. papaya &lt; A. vasica &lt; C. nutans.DOI: http://dx.doi.org/10.3329/icpj.v2i8.15588 International Current Pharmaceutical Journal, July 2013, 2(8): 131-140