Animal Carcinogenicity Research Articles

Occupational exposure of aldehydes resulting from the storage of wood pellets

ABSTRACTAn exposure assessment was conducted to investigate the potential for harmful concentrations of airborne short chain aldehydes emitted from recently stored wood pellets. Wood pellets can emit a number of airborne aldehydes include acetaldehyde, formaldehyde, propionaldehyde, butyraldehyde, valeraldehyde, and hexanal. Exposure limits have been set for these compounds since they can result in significant irritation of the upper respiratory system at elevated concentrations. Formaldehyde is a recognized human carcinogen and acetaldehyde is an animal carcinogen. Thus, air sampling was performed in a wood pellet warehouse at a pellet mill, two residential homes with bulk wood pellet storage bins, and in controlled laboratory experiments to evaluate the risk to occupants. Using NIOSH method 2539, sampling was conducted in five locations in the warehouse from April–June 2016 when it contained varying quantities of bagged pellets as well as two homes with ten ton bulk storage bins. The aldehyde concentrations were found to increase with the amount of stored pellets. Airborne concentrations of formaldehyde were as high as 0.45 ppm in the warehouse exceeding the NIOSH REL-C, and ACGIH TLV-C occupational exposure limits (OELs). The concentrations of aldehydes measured in the residential bins were also elevated indicating emissions may raise indoor air quality concerns for occupants. While individual exposures are of concern the combined irritant effect of all the aldehydes is a further raise the concerns for building occupants. To minimize exposure and the risk of adverse health effects to a building's occupants in storage areas with large quantities of pellets, adequate ventilation must be designed into storage areas.

Acetylsalicylic acid application decreased tobacco-specific nitrosamines and its precursors but maintained quality of air-cured burley tobacco (Nicotiana tabacum L.)

Burley tobacco (Nicotiana tabacum L.) is an important raw material in the production of Chinese-style blended cigarettes. However, the high levels of tobacco-specific nitrosamines (TSNA) have devalued the industrial use of burley tobacco and limited its sustainable use. The objective of this paper was to investigate the effects of acetylsalicylic acid (ASA) application on accumulation of TSNA, its precursors and quality of air-cured burley tobacco (Nicotiana tabacum L. cv. DaBai 1). Field experiments were conducted to determine the contents of TSNA and the precursors and the sensory quality of burley tobacco under 0, 0.1, 0.3mM of ASA in 2014 and 2015 at Dazhou, Sichuan Province, China. The results showed that TSNA, nitrate, nitrite and alkaloids levels were significantly reduced by the application of ASA, of which the total TSNA were significantly lower by 10.40–24.75%, and two of the strong animal carcinogens in tobacco products, i.e. N-nitrosonornicotine (NNN) and 4-(methylnitrosamino) -1- (3- pyridyl) -1- butanone (NNK) were reduced by 9.01–24.23% and 11.43–26.86%, respectively. Year had significant effects on TSNA and the TSNA contents in 2014 were higher than in 2015. Interestingly, the sensory quality of burley tobacco remained or was even better after application of ASA. In conclusion, this study revealed that ASA application was able to reduce the levels of TSNA and its precursors in sustaining burley tobacco industry potentially.

2-Year animal carcinogenicity results for crisaborole, a novel phosphodiesterase 4 inhibitor for atopic dermatitis

BackgroundCrisaborole is a novel, topical nonsteroidal, anti-inflammatory, phosphodiesterase 4 (PDE4) inhibitor for the treatment of mild to moderate atopic dermatitis. ObjectiveAs part of a nonclinical safety testing program, these 2-year studies tested the carcinogenic potential of crisaborole. MethodsCrisaborole ointment, 2%, 5%, or 7%, was applied once daily topically to mice, and crisaborole was administered orally to rats at doses of 30, 100, or 300mg/kg/day for up to 104 weeks. Systemic exposure to crisaborole and its metabolites, moribundity/death, clinical signs, and tumor formation were assessed in each study. ResultsCrisaborole treatment was not tumorigenic in mice at any of the doses administered and did not increase the incidence of neoplastic or nonneoplastic microscopic lesions compared with controls. Oral administration of crisaborole at the high dose (300mg/kg/day) to female rats increased the incidence of treatment-related benign granular cell tumors in the distal reproductive tract (uterus with cervix and vagina) but did not cause moribundity/death. ConclusionCrisaborole was well tolerated and not tumorigenic in mice. It was not tumorigenic in male rats at 300mg/kg/day at exposures that were 3× the human area under the concentration-time curve (AUC24) and was nontumorigenic in female rats at 100mg/kg/day at exposures that were 1× the human AUC24.

Acrylamide in Stir-fried Potato and Onion for Simmered Dishes in Japan.

Acrylamide has neurotoxicity, carcinogenicity, and genotoxicity in experimental animals and cellular systems. Fried potato is one of the major intake sources of acrylamide in food, and fried onion was reported to contain up to 100 ng/g level of acrylamide. To determine acrylamide concentration in potato and onion stir-fried prior to boiling for simmered dishes such as curry, stew, and Niku-jaga, a typical Japanese meat/potato/onion cuisine, we collected samples stir-fried at homes of volunteers who intended voluntarily to cook these simmered dishes. Acrylamide level was analyzed by GC-MS after the xanthydrol derivatization. Among 53 stir-fried potato samples, median and average values of acrylamide were found to be 2.0 ng/g and 11 ng/g, respectively. Acrylamide levels of 27 samples (51%) were less than limit of detection (LOD) (4 ng/g), and those of 13 samples (25%) were less than limit of quantification (LOQ) (10 ng/g). In cases with less than LOD and less than LOQ of acrylamide levels, one-half of LOD and average of LOD and LOQ were adopted, respectively, to calculate the median and average. This median was markedly lower than those of fried potato (180 ng/g) and potato snacks including potato chips (550 ng/g) reported in monitoring in 2013 fiscal year in Japan. Among 58 stir-fried onion samples, acrylamide level of only one sample (2%) was less than LOD (3 ng/g), and those of 15 samples (26%) were less than LOQ (8 ng/g). The median and average values in the stir-fried onion were 14 ng/g and 36 ng/g, respectively. These values are comparable to those for stir-fried onion reported by Ministry of Agriculture, Forestry and Fisheries, Japan (median 19 ng/g, average 25 ng/g). But the maximum value of stir-fried onion 420 ng/g in the present study is much higher than the reported maximum value (70 ng/g).

The genotoxic potency of glycidol established from micronucleus frequency and hemoglobin adduct levels in mice

Glycidol is a genotoxic animal carcinogen that has raised concern due to its presence in food, as glycidyl fatty acid esters. Here we investigated the genotoxicity of glycidol in BalbC mice (0–120 mg/kg) by monitoring the induction of micronuclei in peripheral blood as a marker of chromosomal damage. The scoring of the micronuclei was assessed by flow cytometry. In the treated mice, the internal dose of glycidol, expressed as area under the concentration-time curve, AUC (mol × L−1 × h; Mh), was measured by dihydroxypropyl adducts to hemoglobin (Hb). The study showed that glycidol induced linear dose-dependent increases of Hb adducts (20 pmol/g Hb per mg/kg) and of micronuclei frequencies (12‰ per mMh).Compared to calculations based on administered dose, an improved dose-response relationship was observed when considering internal dose, achieved through the applied combination of sensitive techniques used for the scoring of micronuclei and AUC estimation of glycidol in the same mice. By comparing with earlier studies on micronuclei induction in mice exposed to ionizing radiation we estimated the radiation dose equivalent (rad-eq.) of glycidol to be ca 15 rad-eq./mMh.

Context Matters: Contribution of Specific DNA Adducts to the Genotoxic Properties of the Tobacco-Specific Nitrosamine NNK.

The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a potent pulmonary carcinogen in laboratory animals. It is classified as a Group 1 human carcinogen by the International Agency for Cancer Research. NNK is bioactivated upon cytochrome P450 catalyzed hydroxylation of the carbon atoms adjacent to the nitrosamino group to both methylating and pyridyloxobutylating agents. Both pathways generate a spectrum of DNA damage that contributes to the overall mutagenic and toxic properties of this compound. NNK is also reduced to form 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), which is also carcinogenic. Like NNK, NNAL requires metabolic activation to DNA alkylating agents. Methyl hydroxylation of NNAL generates pyridylhydroxybutyl DNA adducts, and methylene hydroxylation leads to DNA methyl adducts. The consequence of this complex metabolism is that NNK generates a vast spectrum of DNA damage, any form of which can contribute to the overall carcinogenic properties of this potent pulmonary carcinogen. This Perspective reviews the chemistry and genotoxic properties of the collection of DNA adducts formed from NNK. In addition, it provides evidence that multiple adducts contribute to the overall carcinogenic properties of this chemical. The adduct that contributes to the genotoxic effects of NNK depends on the context, such as the relative amounts of each DNA alkylating pathway occurring in the model system, the levels and genetic variants of key repair enzymes, and the gene targeted for mutation.

Biotransformation of chromium (Cr-VI to Cr III) from tannery effluent using bacteria and fungi

Chromium, a priority pollutant is well known for its mutagenicity, carcinogenicity and teratogenicity in humans, animals and plants. Extensive use of chromium in industries such as leather tanning, stainless -steel production, electroplating and wood preservatives have resulted in extensive chromium contaminated soil and ground water. Microorganisms are involved in the removal of toxic wastes, both in the natural environment and in controlled treatment systems. The present study was undertake n to optimize the chromium reduction capabilities of microbes isolated from the tannery effluents of Dindigul district. About 68 bacterial and 23 fungal isolates were identified based on their microscopic and macroscopic features. The screening was done on minimal salt media incorporated with potassium dichromate. The Bacillus amyloliquefaciensCRB36 strain showed the maximum chromium reduction activity when compared to other bacterial and fungal species isolated in this study. The optimization of chromium reduction was done using various physico-chemical parameters. In the optimization study, the best condition for the reduction of toxic form of chromium was achieved when starch and peptone were supplied as carbon and nitrogen sources at an optimum pH of 7.0 with an incubation temperature of 30°C. Bioremediation is the most promising, eco -friendly and cost effective technology widely used now a days for detoxification of toxic industrial pollutants in soil and water.

An overview of the toxicology and toxicokinetics of fusarenon-X, a type B trichothecene mycotoxin.

Fusarenon-X (FX) is a type B trichothecene mycotoxin that is frequently observed along with deoxynivalenol (DON) and nivalenol (NIV) in agricultural commodities. This review aims to give an overview of the literature concerning the toxicology and toxicokinetics of FX. FX is primarily found in cereals grown in temperate regions, but it can also be found worldwide because of the global transport of products. The major toxicity of FX occurs through inhibition of protein synthesis, followed by the disruption of DNA synthesis. Moreover, FX has also been shown to induce apoptosis in in vitro and in vivo studies. The targets of FX are organs containing actively proliferating cells, such as the thymus, spleen, skin, small intestine, testes and bone marrow. FX causes immunosuppression, intestinal malabsorption, developmental toxicity and genotoxicity. In addition, sufficient evidence of carcinogenicity in experimental animals is currently lacking, and the International Agency for Research on Cancer (IARC) classifies it as a group 3 carcinogen.

Long-Term Stability of Volatile Nitrosamines in Human Urine

Volatile nitrosamines (VNAs) are established teratogens and carcinogens in animals and classified as probable (group 2A) and possible (group 2B) carcinogens in humans by the IARC. High levels of VNAs have been detected in tobacco products and in both mainstream and sidestream smoke. VNA exposure may lead to lipid peroxidation and oxidative stress (e.g., inflammation), chronic diseases (e.g., diabetes) and neurodegenerative diseases (e.g., Alzheimer's disease). To conduct epidemiological studies on the effects of VNA exposure, short-term and long-term stabilities of VNAs in the urine matrix are needed. In this report, the stability of six VNAs (N-nitrosodimethylamine, N-nitrosomethylethylamine, N-nitrosodiethylamine, N-nitrosopiperidine, N-nitrosopyrrolidine and N-nitrosomorpholine) in human urine is analyzed for the first time using in vitro blank urine pools fortified with a standard mixture of all six VNAs. Over a 24-day period, analytes were monitored in samples stored at ∼20°C (collection temperature), 4-10°C (transit temperature) and -20 and -70°C (long-term storage temperatures). All six analytes were stable for 24 days at all temperatures (n = 15). The analytes were then analyzed over a longer time period at -70°C; all analytes were stable for up to 1 year (n = 62). A subset of 44 samples was prepared as a single batch and stored at -20°C, the temperature at which prepared samples are stored. These prepared samples were run in duplicate weekly over 10 weeks, and all six analytes were stable over the entire period (n = 22).

Multiple contrast type tests for the evaluation of animal carcinogenicity studies

ABSTRACTThe Cochran–Armitage (CA) test is frequently used for testing the dose–response relationship in tumor incidence. This test is based on a weighted linear regression of proportions. It is well known that the CA test lacks power for nonlinear tumor outcomes. For general shape of outcomes, Hothorn and Bretz (2000) proposed a multiple contrast (MC) test. This test suggests the use of the maximum over several single contrasts, where each of them is chosen appropriately to cover a specific dose–response shape. In this work, two new test procedures are proposed and they are compared to the CA and MC tests using power.

Colorectal cancer risk and nitrate exposure through drinking water and diet

Ingested nitrate leads to the endogenous synthesis of N-nitroso compounds (NOCs), animal carcinogens with limited human evidence. We aimed to evaluate the risk of colorectal cancer (CRC) associated with nitrate exposure in drinking water and diet. A case-control study in Spain and Italy during 2008-2013 was conducted. Hospital-based incident cases and population-based (Spain) or hospital-based (Italy) controls were interviewed on residential history, water consumption since age 18, and dietary information. Long-term waterborne ingested nitrate was derived from routine monitoring records, linked to subjects' residential histories and water consumption habits. Dietary nitrate intake was estimated from food frequency questionnaires and published food composition databases. Odd ratios (OR) were calculated using mixed models with area as random effect, adjusted for CRC risk factors and other covariables. Generalized additive models (GAMs) were used to analyze exposure-response relationships. Interaction with endogenous nitrosation factors and other covariables was also evaluated. In total 1,869 cases and 3,530 controls were analyzed. Average waterborne ingested nitrate ranged from 3.4 to 19.7 mg/day, among areas. OR (95% CIs) of CRC was 1.49 (1.24, 1.78) for >10 versus ≤5 mg/day, overall. Associations were larger among men versus women, and among subjects with high red meat intake. GAMs showed increasing exposure-response relationship among men. Animal-derived dietary nitrate was associated with rectal, but not with colon cancer risk. In conclusion, a positive association between CRC risk and waterborne ingested nitrate is suggested, mainly among subgroups with other risk factors. Heterogeneous effects of nitrate from different sources (water, animal and vegetables) warrant further research.

Extremely low-frequency magnetic fields and risk of childhood leukemia: A risk assessment by the ARIMMORA consortium.

Exposure to extremely low-frequency magnetic fields (ELF-MF) was evaluated in an International Agency for Research on Cancer (IARC) Monographs as "possibly carcinogenic to humans" in 2001, based on increased childhood leukemia risk observed in epidemiological studies. We conducted a hazard assessment using available scientific evidence published before March 2015, with inclusion of new research findings from the Advanced Research on Interaction Mechanisms of electroMagnetic exposures with Organisms for Risk Assessment (ARIMMORA) project. The IARC Monograph evaluation scheme was applied to hazard identification. In ARIMMORA for the first time, a transgenic mouse model was used to mimic the most common childhood leukemia: new pathogenic mechanisms were indicated, but more data are needed to draw definitive conclusions. Although experiments in different animal strains showed exposure-related decreases of CD8+ T-cells, a role in carcinogenesis must be further established. No direct damage of DNA by exposure was observed. Overall in the literature, there is limited evidence of carcinogenicity in humans and inadequate evidence of carcinogenicity in experimental animals, with only weak supporting evidence from mechanistic studies. New exposure data from ARIMMORA confirmed that if the association is nevertheless causal, up to 2% of childhood leukemias in Europe, as previously estimated, may be attributable to ELF-MF. In summary, ARIMMORA concludes that the relationship between ELF-MF and childhood leukemia remains consistent with possible carcinogenicity in humans. While this scientific uncertainty is dissatisfactory for science and public health, new mechanistic insight from ARIMMORA experiments points to future research that could provide a step-change in future assessments. Bioelectromagnetics. 37:183-189, 2016. © 2016 Wiley Periodicals, Inc.

Ingested Nitrate and Breast Cancer in the Spanish Multicase-Control Study on Cancer (MCC-Spain).

Background:Ingested nitrate leads to endogenous formation of N-nitroso compounds that are breast carcinogens in animals, but human evidence is limited.Objective:We evaluated ingested nitrate as a risk factor for breast cancer (BC) in a multicase–control study.Methods:Hospital-based incident BC cases and population-based controls were recruited in eight Spanish regions in 2008–2013; participants provided residential and water consumption from 18 years of age and information on known BC risk factors. Long-term nitrate levels (1940–2010) were estimated and linked with residential histories and water consumption to calculate waterborne ingested nitrate (milligrams/day). Dietary ingested nitrate (milligrams/day) was calculated using food frequency questionnaires and published dietary nitrate contents. Interactions with endogenous nitrosation factors and other variables were evaluated. A total of 1,245 cases and 1,520 controls were included in the statistical analysis.Results:Among the study regions, average ± SD waterborne ingested nitrate ranged from 2.9 ± 1.9 to 13.5 ± 7.5 mg/day, and dietary ingested nitrate ranged from 88.5 ± 48.7 to 154 ± 87.8 mg/day. Waterborne ingested nitrate was not associated with BC overall, but among postmenopausal women, those with both high nitrate (> 6 vs. < 2.6 mg/day) and high red meat intake (≥ 20 vs. < 20 g/day) were more likely to be cases than women with low nitrate and low red meat intake (adjusted odds ratio = 1.64; 95% confidence interval: 1.08, 2.49; overall interaction p-value = 0.17). No association was found with dietary nitrate.Conclusions:Waterborne ingested nitrate was associated with BC only among postmenopausal women with high red meat consumption. Dietary nitrate was not associated with BC regardless of the animal or vegetable source or of menopausal status.Citation:Espejo-Herrera N, Gracia-Lavedan E, Pollan M, Aragonés N, Boldo E, Perez-Gomez B, Altzibar JM, Amiano P, Zabala AJ, Ardanaz E, Guevara M, Molina AJ, Barrio JP, Gómez-Acebo I, Tardón A, Peiró R, Chirlaque MD, Palau M, Muñoz M, Font-Ribera L, Castaño-Vinyals G, Kogevinas M, Villanueva CM. 2016. Ingested nitrate and breast cancer in the Spanish Multicase-Control Study on Cancer (MCC-Spain). Environ Health Perspect 124:1042–1049; http://dx.doi.org/10.1289/ehp.1510334

Toxicity and Carcinogenicity of Dichlorodiphenyltrichloroethane (DDT).

Dichlorodiphenyltrichloroethane (DDT) is still used in certain areas of tropics and subtropics to control malaria and other insect-transmitted diseases. DDT and its metabolites have been extensively studied for their toxicity and carcinogenicity in animals and humans and shown to have an endocrine disrupting potential affecting reproductive system although the effects may vary among animal species in correlation with exposure levels. Epidemiologic studies revealed either positive or negative associations between exposure to DDT and tumor development, but there has been no clear evidence that DDT causes cancer in humans. In experimental animals, tumor induction by DDT has been shown in the liver, lung, and adrenals. The mechanisms of hepatic tumor development by DDT have been studied in rats and mice. DDT is known as a non-genotoxic hepatocarcinogen and has been shown to induce microsomal enzymes through activation of constitutive androstane receptor (CAR) and to inhibit gap junctional intercellular communication (GJIC) in the rodent liver. The results from our previously conducted 4-week and 2-year feeding studies of p,p′-DDT in F344 rats indicate that DDT may induce hepatocellular eosinophilic foci as a result of oxidative DNA damage and leads them to hepatic neoplasia in combination with its mitogenic activity and inhibitory effect on GJIC. Oxidative stress could be a key factor in hepatocarcinogenesis by DDT.

Expression of a constitutively active nitrate reductase variant in tobacco reduces tobacco-specific nitrosamine accumulation in cured leaves and cigarette smoke.

SummaryBurley tobaccos (Nicotiana tabacum) display a nitrogen‐use‐deficiency phenotype that is associated with the accumulation of high levels of nitrate within the leaf, a trait correlated with production of a class of compounds referred to as tobacco‐specific nitrosamines (TSNAs). Two TSNA species, 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanone (NNK) and N‐nitrosonornicotine (NNN), have been shown to be strong carcinogens in numerous animal studies. We investigated the potential of molecular genetic strategies to lower nitrate levels in burley tobaccos by overexpressing genes encoding key enzymes of the nitrogen‐assimilation pathway. Of the various constructs tested, only the expression of a constitutively active nitrate reductase (NR) dramatically decreased free nitrate levels in the leaves. Field‐grown tobacco plants expressing this NR variant exhibited greatly reduced levels of TSNAs in both cured leaves and mainstream smoke of cigarettes made from these materials. Decreasing leaf nitrate levels via expression of a constitutively active NR enzyme represents an exceptionally promising means for reducing the production of NNN and NNK, two of the most well‐documented animal carcinogens found in tobacco products.

Lycopene Protects the Diabetic Rat Kidney Against Oxidative Stress-mediated Oxidative Damage Induced by Furan

Furan is a food and environmental contaminant and a potent carcinogen in animals. Lycopene is one dietary carotenoid found in fruits such as tomato, watermelon and grapefruit. The present study was designed to explore the protective effect of lycopene against furan-induced oxidative damage in streptozotocin (STZ)-induced diabetic rat kidney. At the end of the experimental period (28 days), we found that lycopene markedly decreased the malondialdehide (MDA) levels in the kidney, urea, uric acid and creatinine levels in the serum of furan-treated rats. The increase of histopathology in the kidney of furan-treated rats were effectively suppressed by lycopene. Furthermore, lycopene markedly restored superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) activities in the kidney of furan-treated rats. In conclusion, these results suggested that lycopene could protect the rat kidney against furan-induced injury by improving renal function, attenuating histopathologic changes, reducing MDA production and renewing the activities of antioxidant enzymes.

Induction of tyrosine aminotransferase in mice is inhibited by the activated metabolites of ortho-aminoazotoluene

Aminoazo dyes and other hepatocarcinogenic substances inhibit glucocorticoid-mediated induction of adaptive enzymes, including tyrosine aminotransferase (TAT), in the liver of mice and rats. There is a specific relationship between the effect of a carcinogen on TAT induction and its liver carcinogenicity in animals. If the presumption that tumors are caused not by the chemicals employed but their metabolically activated derivatives is correct, the question arises whether TAT induction is inhibited by carcinogen metabolites or the initial compounds. The goal of this paper is to shed some light on the issue. Mice strains differing in sensitivity to both the carcinogenic and antiglucocorticoid (inhibits TAT induction) effects of the mouse-specific carcinogen ortho-aminoazotoluene (OAT) underwent a set of experimental procedures: ablation of sex and adrenal glands, administration of inhibitors (CoCl2 and pentachlorophenol) or inducers (3,4-benzopyrene, Aroclor 1254, and 20-methylcholanthrene) of xenobiotic-metabolizing enzyme activities, etc. The results unequivocally confirm that glucocorticoid induction of TAT activity in the mouse liver is inhibited by the activated OAT metabolite(s) rather than its initial molecules. In contrast, nonspecific genotoxic agents such as cyclophosphamide and cisplatin exert no effect on TAT induction by glucocorticoids. The wide occurrence (practically in each TAT-expressing hepatocyte) and rapidly reversible inhibition of the enzyme induction by the carcinogen point to the epigenetic nature of this phenomenon.

In vitro toxicological evaluation of ethyl carbamate in human HepG2 cells.

Ethyl carbamate (EC) is a multi-site carcinogen in experiment animals and probably carcinogenic to humans (IARC group 2A). The present study was designed to investigate the cytotoxicity effect of EC on human hepatoma G2 (HepG2) cells. The results revealed that EC inhibited the viability of HepG2 cells significantly in a dose-dependent manner. Further analysis indicated that high concentration of EC induced cell apoptosis, inhibited the G1 to S phase transition along with increased expression of p53 and p21 and decreased the expression of cyclin E and Cdk 2, but no significant change in p27 expression was observed, which were evidenced by both real time PCR and western blotting analyses. Moreover, the results of the DCFH-DA assay suggested that oxidative stress was involved in the cytotoxic effects of EC. Altogether, the present work indicated that p21, cyclin E and Cdk2, which were regulated by p53, might account for the effect of EC on cell viability and cell cycle arrest, but p27 was not involved in the pathway in HepG2 cells treated with EC.

Heterocyclic aromatic amines and their contribution to the bacterial mutagenicity of the particulate phase of cigarette smoke.

Heterocyclic aromatic amines (HAAs) rank among the strongest known mutagens. Approximately 30 HAAs have been found in cooked foods (broiled, fried, and grilled) and several HAAs have been characterized as animal carcinogens. Nine HAAs have also been reported to be constituents of cigarette smoke (CS) raising concerns that HAAs might contribute significantly to the known carcinogenicity of CS. As HAAs are found predominantly in the total particulate matter (TPM) of CS, an improved method for the quantification of HAAs in TPM is reported allowing detection and quantification of 8 HAAs in a single run. The mutagenic potency of these HAAs and that of TPM from the reference cigarette 2R4F was determined in the Salmonella Reverse Mutation Assay (Ames assay) with tester strain TA98 and a metabolic activation system. The 8 HAAs, when applied together in the Ames assay, showed a clear sub-additive response. Likewise, the combination of HAAs and TPM, if at all, gave rise to a slight sub-additive response. In both cases, however, the sub-additive response in the Ames assay was observed at HAA doses that are far above the amounts found in CS. The contribution of the individual HAAs to the total mutagenic activity of TPM was calculated and experimentally confirmed to be approximately 1% of the total mutagenic activity. Thus, HAAs do not contribute significantly to the bacterial in vitro mutagenicity of CS TPM.

Optimization of process variables for hexavalent chromium biosorption by psychrotrophic Pseudomonas putida SKG-1 isolate

Hexavalent chromium, a priority pollutant, is well known for its carcinogenicity, mutagenicity, and teratogenicity in humans, animals, and plants. Biosorption is an attractive technique for the treatment of chromium pollution. This study was aimed to optimize the effect of various process parameters on biosorption of Cr6+ by Pseudomonas putida SKG-1 employing conventional one-factor-at-a-time and response surface methodology (RSM) approaches in a batch process. In conventional method, the maximum Cr6+ biosorption (97%) was achieved at 6.0g dead cell biomass l−1, pH 3.0, and 35°C during 195 min contact time with an initial Cr6+ concentration of 50 mg l−1 under shaking (150 rpm). Whereas in RSM approach, a slightly enhanced Cr6+ biosorption (98%) was obtained only in 180 min by P. putida cells (8.0g l−1). The correlation coefficient (R2) of biosorption data to Cr6+ simulated by the Langmuir, Freundlich, and D–R isotherm models was 0.9953, 0.8482, and 0.8916, respectively. The best fit was obtained for Langmuir model which suggests the binding of chromium as a monolayer on the surface of the biomass.