ISSN:0893-6692    

DOI:10.1002/em.2850210302

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractSeveral mammalian repetitive transposable genetic elements were characterized in recent years, and their role in mutagenesis is delineated in this review. Two main groups have been described: elements with symmetrical termini such as the murine IAP sequences and the human THE 1 elements and elements characterized by a poly‐A rich tail at the 3′ end such as the SINE and LINE sequences. The characteristic property of such mobile elements to spread and integrate in the host genome leads to insertional mutagenesis. Both germline and somatic mutations have been documented resulting from the insertion of the various types of mammalian repetitive transposable genetic elements. As foreseen by Barbara McClintock, such genetic events can cause either the activation or the inactivation of specific genes, resulting in their identification via an altered phenotype. Several disease states, such as hemophilia and cancer, are the result of this apparent aspect of genome instability. © 1993 Wiley‐Lis

ISSN:0893-6692    

DOI:10.1002/em.2850210303

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractReactive oxygen species were generated in the gas phase by photosensitization involving illumination of Rose Bengal. Depending on whether the chromophore is dry or solubilized, this system produces either energy‐transfer reactions leading to generation of singlet oxygen specifically, or a combination of energy‐transfer and electron‐transfer reactions, providing both singlet oxygen and reduced forms of oxygen, such as superoxide anion and hydrogen peroxide. In neither case were the reactive species mutagenic in strain TA104 of Salmonella typhimurium, which had been previously shown to be reverted by oxygen species generated by the hypoxanthine‐xanthine oxidase system in aqueous medium. However, mixed oxygen species induced an increased lethality in a variety of DNA repair‐deficient Escherichia coli strains. This genotoxic effect, mainly reparable by the uvrA and recA mechanisms, was efficiently prevented by the thiol N‐acetyl‐L‐cysteine. Singlet oxygen itself failed to exert direct genotoxic effects, although secondary reactants produced by its reaction with cell components enhanced lethality in some repair‐deficient bacteria. Distance‐dependence analyses provided measurements of the lifetimes of the oxygen species generated in the gas phase. ©

ISSN:0893-6692    

DOI:10.1002/em.2850210304

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractThe identification of desmutagens and bioantimutagens in plants has prompted the search for additional plant extracts capable of modifying adverse cellular effects of environmental toxicants. The protective action of crude extracts of Phyllanthus emblica fruits (PFE) against lead (Pb) and aluminium (Al)‐induced sister chromatid exchanges (SCEs) was studied in bone marrow cells of Mus musculus. The modifying effect of the crude extract was compared with that of comparable amounts of synthetic ascorbic acid (AA), a major component of the fruits. Oral administration of PFE or AA for 7 consecutive days before exposure of mice to the metals by intraperitoneal injections reduced the frequencies of SCEs induced by both metals. PFE afforded a more pronounced protective effect than AA in counteracting the genotoxicity induced by both Al and Pb: This difference was significant with Pb. The higher protection afforded by PFE may be attributed to the interaction of AA with other natural ingredients present in the crude fruit extract. ©1993 Wiley‐Liss,

ISSN:0893-6692    

DOI:10.1002/em.2850210305

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractMonochloramine has been suggested as an alternative disinfectant to chlorine to reduce levels of trihalomethanes in treated drinking water, but little is known of the toxicological properties and potential health implications of by‐products specific to the chloramination process. Model aqueous fulvic acid solutions (200–400 mg C/liter), serving as surrogates for humic surface waters, were chloraminated over a range of molar Cl:C ratios from 1:40 to 1:2. The resulting by‐products were extracted into diethyl ether at pH 2 and investigated with the Ames plate incorporation assay. Extractable mutagenicity increased with increasing chlorine and carbon dose up to about 30,000 revertants/liter at Cl:C ratios of 1:2. Mutagenicity was higher inSalmonella typhimuriumstrain TA100 than in strain TA98, and was decreased in the presence of S9, indicating that the mutagens formed were direct‐acting and induced predominantly base‐pair substitutions. Bovine serum albumin decreased slightly, and glutathione reduced greatly, the mutagenic activity detected in extracts. HPLC fractionation of the by‐products indicated that most of the mutagenic activity was found in the earliest‐eluting (most polar) fraction. The mutagenic by‐products appeared to be qualitatively similar to 3‐chloro‐4‐dichlorome‐thyl‐5‐hydroxy‐2‐(5H)‐furanone (MX) in their chromatographic behavior and responses to glutathione and bovine serum albumin, but were less readily detoxified by S9 th

ISSN:0893-6692    

DOI:10.1002/em.2850210306

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractWe examined the mutagenicity ofiso‐butyl nitrite (IBM) vapor and aqueous IBN solution in the Ames test to help evaluate the hazard of sniffing this vapor, a habit which might play a role in the induction of Kaposi's sarcoma associated with acquired immune deficiency syndrome. Chemical analysis showed that the saturated vapor contained 190 μg IBM/ml at 25°C, and saturated aqueous solution, 2.6 mg IBN/ml at 2J‐23°C When agar plates containingSalmonella typhimuriumTA‐1535 and rat liver S‐9 were exposed to IBN vapor, the number of mutants reached a maximum after 40 min. A mean of 307 mutants/plate (22 × background) was observed when the plates were exposed to IBN vapor for 30 min. Addition of 0.2 ml saturated IBN solution in water to similar plates gave a mean of 179 mutants/plate (7.9 × background) in the absence of S‐9, confirming published results. The S‐9 did not affect the results. Based on the IBN level in medium exposed to IBN vapor, the vapor was apparently 11 times more mutagenic than IBN solution. This was attributed to continuous replenishment of unstable IBN in the medium by the vapor. The half‐life of IBN at 21–23°C was>1 hr for solutions in water and<3 min for solutions in the assay medium. This instability was traced to a reaction with phosphate, presumably hydrolysis to nitrite andiso‐butanol. IBN in solution was 2.8 times more mutagenic than sodium nitrite, suggesting that IBN was not mutagenic because of its conversion to nitrite,Iso‐butanol was not mutagenic. The results demonstrate the potential hazard of sniffing IBN vapo

ISSN:0893-6692    

DOI:10.1002/em.2850210307

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractSalmonella typhimuriumstrains TA100, TA104, TA4001, and TA4006 were used to detect the base‐pair mutations caused by six aliphatic epoxides: chloropropylene oxide, glycidyl 1‐naphthyl ether, glycidyl 4‐nitrophenyl ether, 1‐naphthyl‐propylene oxide, styrene oxide, and trichloropropylene oxide. Dose‐mutagenicity relationships could be established for all six epoxides in strains TA100 and TA104 but not in strains TA4001 and TA4006. These results, together with the lack of sensitivity of the TA100 revertants to DL‐1,2,4‐triazole‐3‐alanine, indicate CG→TA transitions and/or CG→AT transversions are of major importance for mutations induced by these epoxides inSalmonellaTA100 and possibly TA104. In addition, since the reproducibility of the effect of the triazole on TA104 reversions was poor, TA→AT transversions were not eliminated as also contributing to the mutagenicity of these epoxides in thisSalmonellastrai

ISSN:0893-6692    

DOI:10.1002/em.2850210308

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractBLM induces DNA degradation in living cells. We used CHO cells with maximal chromatin compactness (cells synchronized in metaphase), cells with chromatin decondensed by Na butyrate treatments, and control cells with normal chromatin condensation in order to analyze the correlation between chromatin compactness, DNA sensitivity to BLM, efficiency of repair of BLM‐induced DNA lesions, and cell viability. We found that the DNA sensitivity to BLM and the efficiency of DNA repair is inversely correlated with the degree of chromatin coiling. Cells with decondensed chromatin are those showing higher DNA sensitivity to BLM but also those having the best efficiency to mend the damage. Accordingly, these cells show an amount of residual DNA lesions and a curve of growth similar to that of control cells. The situation is just the opposite for metaphase cells. The DNA of these cells is more resistant to BLM, but the damage is poorly repaired. The final result is that BLM induces a higher concentration of residual DNA lesions and a lower viability in metaphase than in control cells. Our results suggest that chromatin structure influences the quantity and repairability of the BLM‐induced lesions, producing a higher incidence of double strand break in the DNA of cells with marked chromatin condensation. © 1993 Wiley‐Lis

ISSN:0893-6692    

DOI:10.1002/em.2850210309

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractRiddelliine (RID) is a pyrrolizidine alkaloid found in plants of the genera Crotalaria,Amsinckia, and Senecio in the United States. RID has been extensively studied in a wide variety of in vitro short‐term genotoxicity tests and has yielded positive responses in most test systems; however, there are fewer data available on the effects of RID in in vivo assays and no data under repeat‐dose regimens. We have evaluated the ability of RID to induce unscheduled DNA synthesis (UDS) in hepatocytes, S‐phase synthesis (SPS) in hepatocytes, and micronuclel in bone marrow from animals dosed for 5 or 30 days in conjunction with prechronic toxicity testing conducted for the National Toxicology Program. Results of this study indicate that RID did not induce an increase in micronucleated polychromatic erythrocytes (PCE) in bone marrow of mice after 5 days of dosing or in PCE from rats or mice after 30 days of dosing. RID did not induce an increase in UDS in rat hepatocytes after 5 or 30 days of dosing, but it did induce an equivocal UDS response in male mice after both time points and a positive response in female mice after 30 days of dosing. RID induced significant elevations in SPS in rat hepatocytes after both 5 and 30 days of dosing, even at low doses. An increase in SPS was observed in male and female mouse hepatocytes, but only after 30 days of dosing. Rats and mice of both sexes showed a depression in SPS at higher doses. This effect may be a result of toxicity, which compromises the ability of the liver to regenerate. These results demonstrate that repeated administration of test chemicals may alter the genotoxic response to chemicals. © 1993 Wiley‐L

ISSN:0893-6692    

DOI:10.1002/em.2850210310

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractThe mutagenicity results and data of nine progestins (cyproterone acetate, dehydrospirorenone, gestodene, gestonorone caproate, levonorgestrel, norethisterone, norethisterone acetate, norethisterone enanthate, norethynodrel), one hypothetical metabolite (6,7‐epoxycyproterone acetate), four estrogens (estradiol, ethinylestradiol, cyclotriol, cyclotriol), and four other sex steroids (atamestane, lilopristone, onapristone, propylmesterolone) are reported. All 17 sex steroids were investigated using the Ames salmonella/microsome direct plate incorporation protocol, and seven were additionally tested using the preincubation modification. Seven sex steroids were also studied in the HG‐PRT test with V79 cells for the induction of gene mutations in mammalian cells. The metabolite was examined in the Ames salmonella/microsome assay using the standard protocol and the preincubation modification. In all assays the test compounds were investigated up to concentration levels where cytotoxicity and/or visible precipitation occurred or at least the solubility limit of the test compound was reached. For all assays, evaluation of the data indicates that neither any of the sex steroids nor the hypothetical metabolite was able to induce gene mutations whether in the absence or the presence of an extrinsic metabolizing system (S9 mix). © 1993 Wiley‐Lis

ISSN:0893-6692    

DOI:10.1002/em.2850210311

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY