摘要:

AbstractA recent National Toxicology Program evaluation indicates that the rat hepatocyte/DNA repair assay has a high false‐negative rate and that it is insensitive to some genotoxic hepatocarcinogens as well as other species and organ‐specific carcinogens. In this study, we examined whether the sensitivity of the hepatocyte/DNA repair assay might be increased through animal pretreatment with various hepatic mixed‐function oxidase inducers, i.e., Aroclor 1254, phenobarbital, and 3,3′,4,4′‐tetrachloroazobenzene (TCAB). The effects on unscheduled DNA synthesis (UDS), a measure of DNA damage and repair, were studied in cultures exposed to known and/or potential carcinogens that had been evaluated as negative or questionable or that produced conflicting results with hepatocytes isolated from uninduced animals. 4,4′‐Oxydianiline, 1‐nitropy‐rene, and TCAB produced concentration‐dependent increases in UDS in hepatocytes from rats pretreated with Aroclor 1254. 4,4′‐Oxydianiline and TCAB also induced a dose‐dependent increase in DNA repair in hepatocytes from rats pretreated with phenobarbital, whereas 1‐nitropyrene was negative. 4,4′‐Methylenedianiline produced a marginal response, and 3,3′,4,4′‐tetrachloroazoxybenzene (TCAOB) was negative in Aroclor‐ and pheno‐barbital‐induced hepatocytes; however, TCAOB, as well as TCAB, produced concentration‐dependent increases in UDS in TCAB‐induced hepatocytes. These data indicate that the limited sensitivity to chemical carcinogens displayed by the hepatocyte/DNA repair assay may be increased by using hepatocytes isolated from animals e

ISSN:0893-6692    

DOI:10.1002/em.2850130402

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

年代:1989

数据来源: WILEY

摘要:

AbstractThe in vivo frequency of mutants resulting from mutation at thehprtlocus in human T‐lymphocytes can be determined by a cloning assay. This assay quantifies the frequency of 6‐thioguanine‐resistant (TGr) T‐cells through growth of colonies in 96‐well microtiter dishes. The reproducibility of the TGrmutant frequency values has now been assessed in a longitudinal study of six individuals (three male, three female, aged 22–33 years) employing 4–5 blood samples over a 26–37 week time period. Cloning assays were performed with both fresh and cryopreserved cell samples. No significant differences were found among the mutant frequency values for multiple samples from each individual with both fresh and cryopreserved cell samples. These results demonstrate the reproducibility of this cloning assay for in vivo mutant frequency determinations in huma

ISSN:0893-6692    

DOI:10.1002/em.2850130403

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

年代:1989

数据来源: WILEY

摘要:

AbstractEvidence in the literature from in vitro and in vivo studies as to whether or not radiofrequency radiation (RFR) in the microwave range is mutagenic is predominantly negative, with some positive reports. No evidence is available as to whether RFR will alter the mutagenic activity of genotoxic chemicals during a simultaneous exposure, a likely real‐life situation. Two hypotheses have been proposed: a) that RFR by itself can cause mutations in a mammalian cell in vitro assay system; and b) that a simultaneous exposure to RFR during a chemical treatment of the cells with a known genotoxic agent, mitomycin C (MMC), will alter the extent of mutagenesis induced by the treatment of the cells by the chemical alone. These studies were performed using the forward mutation assay at the thymidine kinase locus in L5178Y mouse leukemic cells. The pulsed wave RFR was broadcast from an antenna horn at a frequency of 2.45 GHz. The power density was 48.8 mW/cm2and the measured specific absorption rate (SAR) in this system was 30 W/kg (600 W forward power), which is well above current safety guidelines. The conclusions from five different experiments, employing three different concentrations of MMC, were that a) RFR exposure alone, at moderate power levels which resulted in a temperature increase in the cell culture medium of less than 3°C, is not mutagenic; and b) when cells are simultaneously treated with MMC and RFR at these same moderate power levels, the RFR does not affect either the inhibition of cell growth or the extent of mutagenesis resulting from the treatment with the chemical MMC alo

ISSN:0893-6692    

DOI:10.1002/em.2850130404

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

年代:1989

数据来源: WILEY

摘要:

AbstractGenetic toxicology studies were conducted on organic dyes and mixtures used in colored smoke munitions. The dyes studied included Solvent Red 1; two different batches (Lot 1 and Lot 2) of Disperse Red 11; terephthalic acid; and a mixture of 25 parts Solvent Red 1, 5 parts Disperse Red 11, and 16 parts terephthalic acid. The dyes were evaluated for their ability to produce mutations inSalmonellabacterial strains and in Chinese hamster ovary (CHO) cells. The dyes were also tested in CHO cells to determine cytotoxicity and the induction of sister chromatid exchanges and chromosome aberration. None of the dyes were genotoxic in the standard Ames assay using bacterial strain TA1535 or TA100 with or without the addition of S‐9 or in TA98 and TA1538 without S‐9. With S‐9, Disperse Red 11 (Lot 2) showed significant mutagenic activity in TA98 and TA1538 which increased as a function of S‐9 concentration. However, the maximum level of mutagenic activity detected was low (3.8 revertants/μg). The azo dye Solvent Red 1 was also negative in a pre‐incubation assay designed to reduce azo compounds to free amines. Solvent Red 1 was cytotoxic to mammalian cells, caused a significant increase in SCE, but was not mutagenic or clastogenic. Disperse Red 11 (Lot 1 and Lot 2) were not cytotoxic or clastogenic but produced an increase in cell cycle time and SCE frequency. Only Disperse Red 11 (Lot 2) increased mutations in the CHO/hypoxanthine‐guanine phosphoribosyltransferase (HGPRT) assay. The mutagenic activity of the dye mixture was not significant, suggesting no synergistic interaction between the dyes. These studies demonstrated that none of the dyes was clastogenic and that a contaminant in Disperse Red 11 (Lot 2) may be responsible for the weak mutagenic activity in both mammalian and bacterial

ISSN:0893-6692    

DOI:10.1002/em.2850130405

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

年代:1989

数据来源: WILEY

摘要:

AbstractThe micronucleus test is used widely as an in vivo short‐term assay for potential carcinogens. In the present study, results of the micronucleus test were affected by the rate of erythropoiesis in the bone marrow erythropoietin, a growth factor for the erythroblast, which was used to induce erythropoiesis.The highest frequency of micronucleated polychromatic erythrocytes (MPCE) and a dose‐response relationship between erythropoietin doses and MPCE frequency were seen 30 hr after injection of 1,1‐dimethylhydrazine (DMH) to mice administered 24 hr previously with erythropoietin. The effect of erythropoietin was maximal when erythropoietin was given 24 hr before DMH, indicating that accelerating the multiplication of erythroblasts will increase the frequency of micronuclei induced by mutagens.Induction of MPCE in the bone marrow by four other compounds—benzo(a)pyrene,2‐naph‐thylamine, mitomycin C, and vincristine—was also increased by pretreatment with e

ISSN:0893-6692    

DOI:10.1002/em.2850130406

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

年代:1989

数据来源: WILEY

摘要:

AbstractChromosome fragility in 96 h, low‐folate cultures was found to be associated with smoking status, coffee consumption, and blood folate level. The higher proportion of cells with chromosome aberrations in cigarette smokers was attributable to lower red cell folate levels in smokers compared with nonsmokers. There was a positive linear relationship between the average cups of coffee consumed per day and the proportion of cells with aberrations. This association was independent of the effects of smoking and red cell folate level. These data suggest that smoking history, coffee consumption, and red cell folate level are important considerations for the design and interpretation of fragile site studies in cancer cytogenetic

ISSN:0893-6692    

DOI:10.1002/em.2850130407

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

年代:1989

数据来源: WILEY

摘要:

AbstractIn vitro assays of the genotoxicity of quinoline compounds have yielded varying indications of their potency, and only limited determinations have been reported following in vivo administrations. We have quantified chromosome aberrations (CA) and sister chromatid exchanges (SCE) in the marrow cells of mice that had been injected with quinoline, 8‐hydroxyquinoline, or 4‐nitroquinoline‐1‐oxide up to levels approaching lethal. Treatments with quinoline produced no consistent increase in the number of aberrations at either 17 or 36 hr after treatment and no significant increase in SCE numbers at either 23 or 42 hr. Similarly, 8‐hydroxyquinoline had no measurable effect on either CA or SCE but did tend to prolong the cell cycle. 4‐Nitroquinoline‐1‐oxide was a very potent inducer of both CA and SCE as well as an inhibitor o

ISSN:0893-6692    

DOI:10.1002/em.2850130408

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

年代:1989

数据来源: WILEY

摘要:

AbstractIdentification of potentially cancer‐causing chemicals is a priority in our society. Short‐term assays for mutation or chromosomal damage, which are rapid, inexpensive, and reproducible, have found widespread use; however, concern has arisen recently because such assays do not coincide completely with the standard rodent bioassay for carcinogenesis. Lack of perfect correlation is not surprising, given the complex, multicausal nature of the carcinogenic process. We have developed methodologies for interpreting short‐term tests to predict carcinogenicity, which allow consideration of the influence of the proportion of carcinogens expected in the tested chemicals, the complexities of the rodent carcinogenesis bioassay, and factors affecting the worth of information. These methodologies are applied to a set of data on genotoxicity and carcinogenicity of 73 chemicals (NTP‐73) recently published by the National Toxicology Program; they illustrate that with this approach, batteries of short‐term tests can indeed be predictive of rodent carcinogenicity or noncarcinogenicity and that batteries are more predictive than theSalmonellaassay alone. The analysis is validated using an additional group of chemicals with results in the same short‐term test

ISSN:0893-6692    

DOI:10.1002/em.2850130409

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

年代:1989

数据来源: WILEY

摘要:

AbstractThree human carcinogens, 4‐aminobiphenyl, treosulphan, and melphalan, were tested for the induction of micronuclei or chromosomal aberrations in the bone marrow cells of male B6C3F1mice. These studies were conducted to provide further information on the in vivo genetic toxicity of compounds known to cause cancer in humans. All three compounds gave positive results in the mouse bone marrow micronucleus test, and melphalan, the only compound tested for aberration induction, was positive in this assay. These results extend the evidence that nearly all known human carcinogens are detected in relatively simple and widely employed short‐term in vivo te

ISSN:0893-6692    

DOI:10.1002/em.2850130410

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

年代:1989

数据来源: WILEY

摘要:

AbstractThe human carcinogen treosulphan was mutagenic inSalmonella typhimuriumTA100 and TA1535, as was dl‐1,2:3,4‐diepoxybutane (DEB), a proposed hydrolysis product of treosulphan. Another proposed hydrolysis product, methane‐ sulfonic acid, was not mutagenic in these strains. The pattern of the mutagenic responses at pH 6, 7, and 8 to treosulphan and DEB suggests that DEB formation may be responsible for the mutagenicity of treosu

ISSN:0893-6692    

DOI:10.1002/em.2850130411

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

年代:1989

数据来源: WILEY