Chromosomal Aberrations In Bone Marrow Cells Research Articles

Hematological, biochemical, genotoxic, and histopathological changes induced by pyridaben.

The current work examined the genotoxic effects of pyridaben (PDB) in male Sprague Dawley rats. Twenty Sprague Dawley rats were divided into four equal groups; the first group was used as a control group; the other three groups were exposed to 19, 28.5, and 57 mg/kg b.w PDB by oral gavage for 4 weeks. Blood samples were collected for hematological and biochemical parameters; femoral bone marrow was flushed for chromosomal aberrations (CA) assay and liver samples were used for the analysis of gene expression of IL-6 and Casp-3 as well as histopathological and immunhistochemical investigation for Casp-3. The results showed that PDB exposure lead to non-significant changes in hematological parameters in all PDB administrated groups while malondialdehyde, glutathione peroxidase, aspartate aminotransferase, and alkaline phosphatase were significantly increased in 19 and 57 mg/kg PDB doses groups Also, gene expression of IL-6 and Casp-3 revealed a significant increase in 28.5 and 57 mg/kg PDB doses groups as compared with the control. However, there was no significant change in the percentage of CAs in bone marrow cells in all PDB-exposed groups. The histopathological and immunhistochemical examination showed focal areas of inflammatory cellular infiltration with fibrosis in 57 mg/kg b.w PDB dose group accompanied by the severe positive reaction of caspase3 in the liver.

Phenolic Compounds of Codiaeum variegatum Spirale Lessened Cytotoxic and Genotoxic Effects of Mitomycin C in Mice Somatic and Germ Cells

This study evaluates the chemopreventive properties of phenolic compounds extracted from Codiaeum variegatum (PCCV) against cytotoxic and genotoxic effects of mitomycin C (MMC). Male Swiss albino mice were treated with PCCV and/or MMC, and samples were collected 24 h after the last treatments. We recorded chromosome aberrations in bone-marrow cells and spermatocytes, cell viability and DNA damage (using comet assay) in bone-marrow cells. We observed that the highest concentration of PCCV did not induce cytotoxic or genotoxic effects on mice somatic and germ cells. However, MMC reduced cell proliferation remarkably (p < 0.05), and increased chromosome aberrations and DNA damage significantly. Additionally, PCCV prohibited cytotoxicity and genotoxicity of MMC when administered to animals 2h prior to MMC. Evidently, PCCV induced a significant inhibition (p < 0.05) in the percentages of chromosome aberrations in bone-marrow cells excluding gaps (19.82, 25.23, and 42.34%) and spermatocytes (22.73, 31.82, and 48.48%) at concentrations 125, 250 and 500 mg/kg b.wt respectively. Likewise, PCCV declined tail DNA (%), tail length (μm) and tail moment, and the inhibitory index of tail DNA (%) reached to 89.44% at 500 mg/kg b.wt. In conclusion, phenolic compounds of Codiaeum variegatum reduced the cytotoxic and genotoxic effects that were induced by the mutagenic agent MMC.

The cytogenetic effects of silibinin alone and in combination with methotrexate in mouse bone marrow

The use of herbal drugs for disease treatment has increased worldwide. Flavonolignan silibinin, the major biologically active component of milk thistle (Silybum marianum), has various biological effects. This study is designed to evaluate the cytogenetic effects of flavonolignan silibinin in mouse bone marrow cells alone and in combination with methotrexate. In this study, the cytogenetic effects of flavonolignan silibinin were observed in mouse bone marrow cells after five days of treatment with a single intraperitoneal (IP) dose of either 50, 100 or 150 mg/kg body weight of silibinin hemisuccinate (SHS), alone or in combination with a single dose of 20 mg/kg methotrexate (MTX). The end-points were chromosomal aberrations (CAs) and a mitotic index (MI) study 24 h after the last dose. SHS (100 mg/kg or 150 mg/kg) could significantly reduce the MI (P < 0.05) in a dose-dependent manner. CAs significantly increased when SHS was administered at 150 mg/kg. Moreover, the MI significantly increased when SHS was administered prior to MTX at 50 mg/kg or 100 mg/kg. However, the MI was further reduced at a dose of 150 mg/kg. Additionally, SHS could significantly reduce the CAs that were induced by MTX. As a conclusion, Silibinin has a weak clastogenic effect, and in combination with MTX, it can enhance MTX's inhibitory effect on the MI and reduce CAs in bone marrow cells. This finding may direct attention to the beneficial effects of using SHS in chemotherapeutic approaches.

English

In the present study the antimutagenic effects of Phyllanthus fruit extract (PFE) has been evaluated against cyclophosphamide induced genotoxicity in bone marrow cells of mice. when animals are treated with different doses of phyllanthus fruit extract i.e., 170,340 and 680 mg/kg to mice, the treated group has not showed any significant increase in the percentage of chromosomal aberrations in bone marrow cells of mice at 48 hrs treatment. A single Intra peritoneal of 50mg/kg of cyclophosphamide induced significant increase in the percentage of chromosomal aberrations in bone marrow cells of mice. However after co administration of three doses of PFE extract there was a dose dependent decrease in the % of micronuclei was observed. When animals were administered with Phyllanthus Fruit Extract PFE 170, 340 & 680 mg/kg/bw orally for seven days and on eightieth day CP (50 mg/kg/bw) was given intraperitonially. For each experimental group control, animals were maintained simultaneously. After the administration of the last dose, the animals were killed and air dried metaphase preparations were made and processed for identification of chromosomal aberrations in somatic cells of mice. In animals treated with single dose of CP, an increase was observed when compared with the values of control group. But when animals primed with PFE + CP group, there was a decrease in the frequency of chromosomal aberrations in somatic cells of mice. Thus the results clearly indicated the protective role of PFE on cyclophosphamide induced genotoxic damage in somatic cells of mice.

Effects of royal jelly on genotoxicity and nephrotoxicity induced by valproic acid in albino mice

Epilepsy is one of the most common neurological diseases affecting at least 50 million people worldwide. Valproic acid (VPA) is a widely used antiepileptic medication for both generalized and partial seizures of epilepsy. The objective of the study was to investigate the anti-mutagenic and anti-histopathologic effects of royal jelly (RJ) on VPA-induced genotoxicity and nephrotoxicity in male albino mice (Mus musculus). 80 Mice were used for 21 days; they were divided into eight groups, (G1) served as normal control group, G2 received VPA (100 mg/kg) and (G3–G5) received RJ at doses 50, 100 and 200 mg/kg respectively. While (G6–G8) were administrated RJ simultaneously with VPA. In RJ treated mice at doses of 50 and 100 mg/kg, the kidney sections showed normal histological structure with non significant changes in chromosomal aberrations (CA) and mitotic index (MI), while RJ at dose of 200 mg/kg showed mild inflammatory cells infiltration and hyperemic glomeruli but not highly significant changes in CA and MI. The cortex of VPA treated mice revealed congested glomeruli with inflammatory cells infiltration, and marked degeneration of almost structures of the glomeruli including some vacuoles in mesangial cells with dark mesangial substances on the ultrastructure level. Some proximal tubules showed degeneration of microvilli on the apical parts of some cells. Cells of the distal tubules attained obliterated lumen and vacuolated lining epithelium. The results also revealed that valproic acid induced a high frequency of CA in bone marrow cells of mice and MI was significantly decreased indicating bone marrow cytotoxicity. The treatment of mice with RJ at doses 50, 100 and 200 mg/kg for 21 days simultaneously with VPA resulted in abating the histological alterations in renal tissues with significant reduction in chromosomal aberrations, for doses of 50 and 100 mg/kg, and elevation in mitotic index (P < 0.05). RJ at doses 50 and 100 mg/kg appeared more potent in exerting the ameliorative effect.

Effects of 100 MeV protons delivered at 0.5 or 1 cGy/min on the in vivo induction of early and delayed chromosomal damage

Little is known about in vivo cytogenetic effects of protons delivered at the dose and dose rates encountered in space. We determined the effects of 100MeV protons, one of the most abundant type of protons produced during solar particle events (SPE), on the induction of chromosome aberrations (CAs) in bone marrow (BM) cells collected at early (3 and 24h) and late (6 months) time-points from groups of BALB/cJ mice (a known radiosensitive strain) exposed whole-body to 0 (sham-controls), 0.5, or 1.0Gy of 100MeV protons, delivered at 0.5 or 1.0cGy/min. These doses and dose-rates are comparable to those produced during SPE events. Additionally, groups of mice were exposed to 0 or 1Gy of 137Cs γ rays (delivered at 1cGy/min) as a reference radiation. The kinetics of formation/reduction of gamma-histone 2-AX (γH2AX) were determined in BM cells collected at 1.5, 3, and 24h post-irradiation to assess the early-response. There were five mice per treatment-group per harvest-time. Our data indicated that the kinetics of γH2AX formation/reduction differed, depending on the dose and dose rate of protons. Highly significant numbers of abnormal cells and chromatid breaks (p<0.01), related to those in sham-control groups, were detected in BM cells collected at each time-point, regardless of dose or dose-rate. The finding of significant increases in the frequencies of delayed non-clonal and clonal CAs in BM cells collected at a late time-point from exposed mice suggested that 0.5 or 1Gy of 100MeV protons is capable of inducing genomic instability in BM cells. However, the extent of effects induced by these two low dose rates was comparable. Further, the results showed that the in vivo cytogenetic effects induced by 1Gy of 100MeV protons or 137Cs γ rays (delivered at 1cGy/min) were similar.

Protection of rat chromosomes by melatonin against gamma radiation-induced damage

The aim of this study was to investigate the protective effect of melatonin (2.5 mg/kg/day, given to rats five times by intra-peritoneal injection) against damage in bone-marrow chromosomes induced by a single dose of gamma radiation (4.0 Gy whole-body irradiation; WBI). Ninety-six male albino rats were divided into four equal groups of 24 rats each. They were designated as I—non-irradiated, non-treated control rats, II—non-irradiated rats treated with melatonin for five successive days, III—whole-body gamma-irradiated rats and IV—rats injected with melatonin daily for five successive days, then subjected to whole-body gamma irradiation 2 h after the final melatonin injection. Six rats from each group were sacrificed at days 1, 3, 7 and 10 following treatment and/or irradiation and their bone marrows were flushed out for micronuclei scoring and chromosomal analysis. WBI resulted in significant elevations in bone-marrow polychromatic erythrocytes containing micronuclei in their cytoplasm, and caused a significant decrease in the mitotic index of bone-marrow cells; in addition, there was a significant increase in the frequency of aberrant bone-marrow cells and in the different types of structural chromosomal aberration. Melatonin injection prior to WBI significantly reduced the mean frequencies of micro-nucleated polychromatic erythrocytes and of aberrant cells, as well as the incidence of structural chromosomal aberrations in bone-marrow cells; it also caused a highly significant elevation in the value of the mitotic index of bone-marrow cells. This investigation clarifies the protective and/or ameliorative role played by melatonin against deleterious effects of gamma radiation.

Genotoxic potential of cyfluthrin

Cyfluthrin (CAS no. 68359-37-5), a synthetic fluorinated pyrethroid insecticide, is widely used in the home environment and in agriculture because of its high activity against a broad spectrum of insect pests and its low animal toxicity. There are no adequate data on genotoxic effects of cyfluthrin. The aim of this study was to analyze the potential genotoxic effects of cyfluthrin. The genotoxicity of cyfluthrin was evaluated, in vitro, by assessing the ability of the insecticide to induce gene mutation (evaluated using the Ames/microsome test), chromosomal aberrations (CA), sister chromatid exchange (SCE) and micronucleus (MN) formation in cultured human peripheral blood lymphocytes. Additionally, CAs and cytotoxicity induced by cyfluthrin were investigated in rat ( Rattus norvegicus var. Albinos) bone-marrow cells to assess in vivo genotoxicity of cyfluthrin. The counts of reverse mutations in Salmonella typhimurium were not significantly increased ( P > 0.05). The frequency of CAs in human lymphocytes, treated with any concentration of cyfluthrin (500, 1000 or 2000 μg/ml) for a 24-h period, was not significantly increased ( P > 0.05). In contrast, CA was significantly increased for the highest two concentrations (1000 and 2000 μg/ml) in the 48-h treatment group compared with the control group (dimethyl sulfoxide, DMSO). Micronucleus formation was significantly ( P < 0.05) increased for all doses after the 48-h treatment, although the frequency of SCE did not increase significantly ( P > 0.05). Mitotic index (MI), proliferation index (PI) and nuclear division index (NDI) decreased significantly ( P < 0.05) due to the potential cytotoxicity of cyfluthrin, especially after the 48-h treatment period. The frequency of chromosome aberrations in bone-marrow cells of rats treated with the test substance increased significantly ( P < 0.05) for all doses (250, 500 and 1000 mg/kg body weight) for the two treatment periods (12 and 24 h) and the two administration routes, viz. intraperitoneal injection (i.p.) and oral gavage (gvg). In vivo cytotoxicity of cyfluthrin was detected only after administration by gavage for the 24-h treatment period. All these findings were not dose-dependent.

The genotoxic effect of potassium metabisulfite using chromosome aberration, sister chromatid exchange, micronucleus tests in human lymphocytes and chromosome aberration test in bone marrow cells of rats

Potassium metabisulfite (PMB) is used as an antimicrobial substance in many kinds of foods. In the present study, the effects of PMB on chromosome aberrations (CAs), sister chromatid exchanges (SCEs), and micronucleus (MN) formation in human lymphocytes and as well as its effect on CAs in bone marrow cells of rats were investigated. The human lymphocytes were treated with 25, 50, 100, and 200 microg/ml of PMB for 24 and 48 hr. PMB was also intraperitoneally (ip) injected to the rats as a single dose of 150, 300, and 600 mg/kg body weight (b.w.) for 12 and 24 hr before sacrifice. PMB induced abnormalities such as structural and numerical (total) CAs, SCEs, and MN formations in a dose dependent manner in the lymphocytes of the 24- and 48-hr treatment periods. In addition, PMB showed a cytotoxic effect by decreasing the replication index (RI), mitotic index (MI) and nuclear division index (NDI) in a dose dependent manner in human lymphocytes. The compound induced CA as well and decreased the MI in bone marrow cells of rats. It might be concluded that PMB had a high genotoxic and cytotoxic risk.

Differences between rodent taxa in fluctuating asymmetry of cranial structures

Fluctuating asymmetry (FA) is undirected differ-ences in the measurements or expression of characterson the right and left sides of the body (R–L). A numberof studies have shown that FA, which is usually treatedas a measure of ontogenetic instability, increases underthe influence of various stress factors. Although thisdependence is not always easily detectable, FA is fre-quently used for the estimation of the population state[1, 2]. At the same time, the nature and evolutionaryimplication of FA remain uncertain [3–5]. It is gener-ally accepted that the genetic control of FA is mainlyprovided by epistatic interactions [6–8]. These interac-tions probably change in the course of evolution(in particular, at early evolutionary stages); therefore, itis reasonable to expect that taxa (in particular, species)would differ in the FA of the same characters. In thisstudy, species and population features of the FA of cra-nial measurements in four rodent species are examinedfrom the evolutionary point of view.Rodent species, sampling points, pollution charac-teristics, and sample sizes are shown in the table. Eachspecies examined is represented by two populationsamples differing in the degree of technogenic stress,including (1) a reference sample, with a relatively lowstress and (2) a sample exposed to a greater impact ofindustries. The population stress was estimated by theaverage frequency of chromosome aberrations in bonemarrow cells. In the reference population of each spe-cies, the frequency of aberrations was significantlylower (χ

Preventive role of aluminosilicate clay against induction of micronuclei and chromosome aberrations in bone-marrow cells of Balb/c mice treated with Zearalenone

Zearalenone (ZEN) is a potent estrogenic metabolite produced by some Fusarium species. No treatment has been successfully employed to remove ZEN contamination in foods. This study was conducted to evaluate the ability of hydrated sodium calcium aluminosilicate (HSCAS) to protect Balb/c mice against cytotoxicity and genotoxicity induced by ZEN. HSCAS was given via the oral route, either alone or simultaneously with a toxic intra-gastric dose of ZEN. The experimental approach comprised treatments of seven groups of mice. The first three groups received 400, 600 or 800 mg/kg bw of HSCAS. Two experimental groups received, respectively, ZEN alone (40 mg/kg bw, representing 8% of the LD 50) and ZEN in combination with HSCAS at 400 mg/kg bw. The two control groups received distilled water and olive oil, respectively. The positive control groups received colchicine (4 mg/kg bw) for the micronucleus assay and mitomycin C (1 mg/kg bw) for the chromosome aberration test. Forty-eight hours after treatment, the femur and tibia were dissected out and analyzed. The results show that ZEN was cytotoxic and genotoxic to Balb/c mice, as indicated by the increase in the frequencies of micronucleated polychromatic erythrocytes (PCEMN) and of chromosomal aberrations in bone-marrow cells. The simultaneous intra-gastric administration of HSCAS with ZEN resulted in a reduction in the number of PCEMN and a decrease of the chromosomal aberration frequency, and an increase in the number of polychromatic erythrocytes (PCE) in bone-marrow cells, compared with those in the group treated with ZEN alone. It could be concluded that HSCAS itself was safe and efficient in the prevention of the toxic effects of ZEN in the gastrointestinal tract.

Clastogenic Effects of the Fasciolicides Closantel and Nitroxynil on Mice Somatic and Germ Cells

Salicylanilide (Closantel) and halogenated phenol (Nitroxynil) have been reported to be an active fasciolocidal agents used in human and in farm animals. The clastogenic effects of Closantel at 5, 10, 15, 20 mg kg−1 b.wt. and Nitroxynil at 10, 20, 30, 40 mg kg−1 b.wt. were tested in mice somatic and germ cells through 3 cytogenetic parameters. Chromosomal aberrations, sister-chromatid exchanges and sperm-shape abnormalities. The results demonstrated that, after intraperitoneal (i.p.) injector with a single doses for 24 h. Closantel and Nitroxynil induced different types of structural chromosomal aberrations in bone-marrow cells which increased significantly with different doses. The frequencies of SCEs were increased significantly with Closantel compared to Nitroxynil induced non-significant frequencies of SCEs except at high dose (40 mg kg−1 b.wt.). The percentage of chromosomal aberrations in diakinesis-metaphase I spermatocytes increased in a dose dependent manner and were found to be statistically significant with the 2 drugs. The 2 fasciolicides induced a signifycant percentage of sperm-shape abnormalities. The highest doses induced 12.74±0.49 and 7.02±0.13 (p<0.01) for closantel and nitroxynil respectively, compared to the control. In conclusion, the 3 cytogenetic parameters used to evaluate the effect of Closantel and Nitroxynil revealed that the 2 fasciolicides have a clastogenic effect on mice somatic and germ cells in vivo studies.

Modification of cyclophosphamide-induced clastogenesis and apoptosis in rats by α-lipoic acid

The aim of the present study was to investigate the protective efficacy of α-lipoic acid (LA) on the cyclophosphamide (CP)-induced chromosomal aberrations (CA) and apoptosis in the bone marrow of rats. Male Wistar rats of 140 ± 20 g were categorized into eight groups. Five groups were administered CP (40 mg/kg body weight, intraperitoneally) to induce toxicity; four of these groups received a single intraperitoneal injection of LA at a dose of either 100 or 200 mg/kg body weight, and either 30 or 60 min prior to CP administration. A vehicle-treated control group and LA control groups were also included. Twenty-four hours after CP treatment, the frequency of CA in bone marrow cells were significantly increased in comparison with the controls. The CP-induced CA were associated with significant increase in DNA damage in the bone marrow as evidenced by increased single strand breaks, whereas in rats treated with LA and CP, the frequency of CA and single strand breaks were significantly decreased in comparison to those given CP alone. CP administration distinctly triggered the apoptotic and necrotic cell death, and LA pretreatment affected cell death by decreasing the number of apoptotic and necrotic cells. The protective effect of LA was found to be stronger at a dose of 200 mg/kg body weight than 100 mg/kg body weight dosage, indicating the dose dependent protective effect of LA. However, the protection by LA was not dependent on the time intervals between LA and CP administration. The results of this study illustrate the protective effect of LA on the CA and apoptosis induced by CP in the erythropoietic system of rats.

Cytogenetic Studies of Berenil in Mice

The antitrypanosomal drug Diminazene aceturate (Berenil) was investigated to assess its genotoxic effect through different cytogenetic parameters. Male swiss mice were intraperitoneal (i.p.) injected with therapeutically relevant doses 3.5, 7 and 10.5 mg kg−1 b.wt. for 1, 3, 5 consecutive days. Berenil increased frequencies of micronucleus in polychromatic erythrocytes especially with high and repeated doses, indicating an aneugenic action. Moreover, marrow toxicity was observed as indicated by significant percentage of chromosome aberrations in bone-marrow cells at all treatment doses. Gaps, fragments and breaks were found to be the most sensitive types of structural aberrations. Polyploidy is a characterized phenomenon of numerical aberrations in treated somatic cells. With respect to germ cells Berenil at the same doses induced high significant percentage of chromosome aberrations (P<0.01) in lry spermatocytes after i.p. treatment with 10.5 mg kg−1 b.wt. for 3 and 5 consecutive days. However, Berenil showed a low influence on sperm abnormalities. Percentage was significant at low level (P<0.05) after the treatment with the highest dose. In conclusion, the different cytogenetic parameters indicate its genotoxic effect on the genome of somatic and germ cells especially at multiple doses.

Clastogenicity of lanthanides: induction of chromosomal aberration in bone marrow cells of mice in vivo

Clastogenic properties of two lanthanide elements praseodymium (Pr) and neodymium (Nd) were evaluated by employing mouse in vivo chromosomal aberrations (CAs) assay. Praseodymium oxide (Pr 6O 11) and neodymium oxide (Nd 2O 3) administered intraperitoneally to Swiss albino mice in vivo induced significant increase in the frequency of CAs in bone marrow cells, when compared to negative control. The number of CAs/cell and percent aberrant cells increased with an increase in the concentration and period of treatment. The effect was maximum when the cells were analysed 12 h after treatment, as compared to 6 and 24 h. This is the first report on the clastogenicity of these elements in mouse in vivo.

Cytogenetic effects of quinalphos in mice

The cytogenetic effect of quinalphos was studied in Swiss albino mice using the micronucleus test, bone marrow and germ cell chromosome assays and sperm morphology assay. Quinalphos at 5, 10 and 15 mg/kg body weight was administered orally to mice. Quinalphos induced micronuclei in the bone-marrow cells of mice and also caused a significant increase in chromosomal aberrations in bone-marrow cells (at 10 and 15 mg/kg body weight dose levels) and in germ cells (at all tested doses). A high incidence of abnormal sperms was also observed in mice treated with quinalphos.

Chromosome aberrations induced by 7,12-dimethylbenz[a]-anthracene in bone marrow cells of spontaneously hypertensive rats (SHR) and control Wistar Kyoto (WKY) rats: time course and site specificity.

The frequency of chromosome aberrations (CA) induced by iv injection of 7,12-dimethylbenz[a]anthracene [(DMBA) CAS: 57-97-6] was examined with the use of control Wistar Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). SHR appear to be analogous to hypertensive humans, since evidence has been reported of a difference in tumor susceptibility between SHR and WKY strains. Injection of DMBA evoked CA in bone marrow cells of both SHR and WKY rats. The frequency of CA in SHR was significantly higher than in WKY rats at 12 and 18 hours after DMBA treatment. With regard to the relative frequencies of aberrations in SHR and WKY rats, chromosomes 1 and 2 were more susceptible to DMBA-induced CA. The proportion of breaks that occur in the "hot spot" at 6 hours after DMBA treatment was distributed nonrandomly at a site approximately 40% of the total length from the centromere in chromosome 1 and at lengths of approximately 30 and 55% in chromosome 2. The specific distribution of CA seemed to be caused by a cell cycle-specific effect. These results, confirming nonrandom CA induced by DMBA in bone marrow cells of WKY rats, are similar to previous reports in which Long-Evans rats were used. Thus they indicate that a common mode of action by DMBA at the chromosome level in rat bone marrow cells was observed in different strains and that SHR were more sensitive than WKY rats to CA induced by DMBA.

Evaluation of the mutagenic potential of four commercial mixtures of insecticides

Male mice (Q strain) were given a single ip injection at the maximum tolerated dose of one of four commercial mixtures of insecticides: Luxan Tue-Taons (150 g dimethoate and 150 g fenitrothion/litre), Metadipterex (210 g trichlorfon and 270 g methyldemeton/litre), Dynafos (155 g malathion, 60 g dichlorvos and 75 g carbaryl/litre) and Phosan Plus (95 g dimethoate, 100 g malathion and 100 g methoxychlor/litre). At the maximum tolerated doses, Luxan Tue-Taons (60 mg/kg), Metadipterex (15 mg/kg), Dynafos (50 mg/kg) and Phosan Plus (100 mg/kg) did not induce chromosome aberrations in bone-marrow cells, spermatogonia or primary spermatocytes of the mice. No evidence of potential genetic effects was obtained in a dominant lethal mutation assay.

Induction of Hepatic Glutathione Transferase and Suppression of 7,12-Dimethylbenz[&lt;italic&gt;a&lt;/italic&gt;]anthracene-Induced Chromosome Aberrations in Rat Bone Marrow Cells by Sudan III and Related Azo Dyes&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;

Noninbred Long-Evans rats fed the reduced form of glutathione (GSH) 2 hours before injection with 7,12-dimethylbenz[a]anthracene [(DMBA) CAS: 57-97-6)] showed a significant suppression of DMBA-induced chromosome aberrations (CA) in bone marrow cells. However, rats given injections of ethyl maleate [(EM) CAS: 141-05-9; (z)-2-butenedioic acid diethyl ester] 0.5 or 2 hours before being killed showed a remarkable fall in the hepatic GSH level. Furthermore, the administration of EM and bromosulfophthalein [CAS: 71-67-0; 3,3'-(4,5,6,7-tetrabromo-3-oxo-1(3H)-isobenzofuranylidene) bis(6-hydroxy)benzenesulfonic acid disodium salt] shortly before the DMBA injection inhibited the suppressive effects of Sudan III on DMBA-induced CA. A clear positive correlation was found between the capacity of Sudan III and related azo dyes to protect against DMBA-induced CA in bone marrow cells and glutathione transferase (GST) activity toward 1-chloro-2,4-dinitrobenzene in the liver cytosol induced by these azo dyes. DMBA activation with hepatic S-9 obtained from rats treated by polychlorinated biphenyls (PCB), phenobarbital, and Sudan III in the Ames system was high in this order as was also the case for the cytochrome P450 content. The addition of GSH to the Ames system containing S-9 from PCB-treated rats resulted in a substantial loss in the mutagenicity of DMBA. The present results suggest that GST and GSH play important roles in DMBA inactivation in rats previously administered Sudan III.

Clastogenic effects of biosynthetic human growth hormone in Snell dwarf mice and CHO cells in vitro

Treatment of Snell dwarf mice with high concentrations of human growth hormone from pituitaries as well as of bacterial origin, significantly increased the frequencies of chromosomal aberrations in bone-marrow cells, as measured by the micronucleus test. In vitro treatment of Chinese hamster ovary (CHO) cells with the two types of hormone likewise induced structural chromosomal aberrations.