摘要:

AbstractPrevious studies have demonstrated marked differences in the capacity of hepatocytes from rats or hamsters to mediate the metabolic activation of chemical carcinogens to genotoxic (ie, mutagenic) products. Thus far, very few investigations of species differences in DNA repair have been performed. Therefore, a comparison of the relative extent of DNA repair elicited by various genotoxic chemicals in rat and hamster hepatocytes was conducted, using the hepatocyte primary culture/DNA repair (HPC/DR) assay. Of the 11 chemicals tested, eight were more potent in inducing DNA repair in hamster hepatocytes than in rat hepatocytes. Dimethylnitrosamine, diethylnitrosamine, 2‐acetylaminofluorene, 9‐aminoacridine, pararosaniline hydrochloride, 1‐naphthylamine, benzidine and 1,2:3,4‐diepoxybutane were all active in hamster hepatocytes at a concentration at least ten times less than the lowest effective concentration in rat hepatocytes. The direct‐acting alkylating agent, methylmethane sulfonate, was equipotent in inducing DNA repair in both rat and hamster hepatocytes, indicating that the differences in DNA repair observed for the other chemicals were probably not a result of species differences in DNA repair capacities. In contrast, 1‐nitropyrene produced a greater DNA repair response in rat hepatocytes than hamster hepatocytes, while the bacterial mutagen 3‐(chloromethyl)pyridine hydrochloride was inactive in both hepatocyte systems. These studies demonstrate the feasibility of using hamster hepatocytes in the HPC/DR assay and illustrate the utility of performing the assay with hepatocytes from more tha

ISSN:0192-2521    

DOI:10.1002/em.2860060102

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

年代:1984

数据来源: WILEY

摘要:

AbstractThe genotoxicity and embryotoxicity of chlorpyrifos (CPF) and two metabolites were evaluated using the chick embryo, Chinese hamster ovary cells, and by examing blastocysts from superovulated cows crossed to chlorpyrifos‐treated bulls. Chlorpyrifos and metabolites were dissolved in acetone and administered to 3‐day embryos by the air cell method. The LD50was 1,500 μg/embryo when mortality was checked through and including 17 days of development. The metabolites were more embryotoxic than the parent compound, CPF. Chlorpyrifos and metabolites did not increase the sister chromatid exchange (SCE) frequency above background at any dosage in the 3‐day chick embryo assay. Similarly, none of these compounds increased SCE frequencies in three‐point dosage tests (1, 10, 100 μg/ml) using Chinese hamster ovary cells. Controls in these assays consisted of the solvent carrier acetone (7.0 ± 2.5 SCE/cell) and 8.6 μg/ml methyl methane sulfonate (30.5 ± 7.4 SCE/cell). Studies of bovine blastocysts obtained from superovulated cows crossed with Dursban 44 treated bulls did not reveal evidence of chromosome aberrations or developmental anomalies associated with pesticide application. However, reproductive performance of breeders may be subnormal as a result of severe poisoning. This underscores the limitations of short‐term assays and emphasizes the need to perform thorough toxicological assays of a chemical according to actual usage patterns in the spec

ISSN:0192-2521    

DOI:10.1002/em.2860060103

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

年代:1984

数据来源: WILEY

摘要:

AbstractThe incidence of sister chromatid exchanges (SCEs) and cell proliferation kinetics have been studied in peripheral blood lymphocytes of man and muntjac grown at 33 to 44 °C to gain insight into SCE formation. The frequency of SCEs increased as a function of growth temperature. At a given temperature, however, the frequency of SCEs varied with the sampling times; the early sampled cells showed fewer SCEs than did those harvested late. At 33 °C the frequency of SCEs was lowest and there was a marked delay in cell‐cycle progression. The number of SCEs was maximum at 40 °C in human and 42 °C in muntjac. Cell proliferation was markedly affected at higher temperature and 44 °C was found to be intolerable for lymphocytes of both the species. It is proposed that certain temperature‐dependent enzyme(s) associated with DNA replication kinetics may be involved in the formation

ISSN:0192-2521    

DOI:10.1002/em.2860060104

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

年代:1984

数据来源: WILEY

摘要:

AbstractA single dose (36 rad) of X rays was given to mouse embryos and neonates that were then treated with urethane at 21 days of age. Although in utero X‐radiation to mice was not tumorigenic, it significantly increased lung tumor susceptibility to a postnataliy‐given carcinogen, urethane. X‐ray induction of persistent hyper‐sensitivity to lung tumorigenesis was apparent at all stages during days 0 to 14 of gestation (except on day 6), but was not observed at late fetal and neonatal

ISSN:0192-2521    

DOI:10.1002/em.2860060105

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

年代:1984

数据来源: WILEY

摘要:

AbstractThe unscheduled DNA synthesis (UDS) technique has been adapted for use in the chick embryo, in vivo, to determine the relationship between induction of the mixed‐function oxidase (MFO) enzyme system and genetic damage from an indirect‐acting mutagen‐carcinogen. Embryos were injected at 6 days of incubation (DI) with either phenobarbital (PB), a specific inducer of P‐450‐associated enzyme activities, or 3,4,3′,4′‐tetrachlorobiphenyl (TCB), a specific inducer of P1‐450‐associated enzyme activities. Aflatoxin B1(AFB1) was injected 24 hr later (7 DI), followed by a 5‐hr continuous3H‐thymidine exposure. The livers were removed, prepared for autoradiography, and hepatocytes were scored for an increase in grains/nucleus, indicative of UDS. Aflatoxin B1caused a dose‐related increase in UDS in all control and induction groups. Phenobarbital‐induced embryos had an increased UDS response while TCB‐induced embryos had a decreased UDS response, relative to noninduced embryos, for each dosage of AFB1. This suggests that the genotoxicity of an indirect‐acting mutagen‐carcinogen can be either increased or decreased, in vivo, depending on the inducer used. The chick embryo provides an excellent system for studying the effect of MFO induction on the genotoxicity of promutagen

ISSN:0192-2521    

DOI:10.1002/em.2860060106

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

年代:1984

数据来源: WILEY

摘要:

AbstractInflorescences fromTradescantiaclones 4430 and 02 were subjected to mean magnetic field intensiteis of 0.16 or 0.76 to 0.78 tesla for 6 to 11 days. Following exposures to both intensities, damage to pollen mother cell chromosomes at early prophase was determined by scoring the frequency of micronuclei in early tetrads. Pink mutations in stamen hair cells of clone 4430 were scored for 15 days after a 6‐day exposure to the higher intensity level while clone 02 was scored during and for 6 days after an 11‐day exposure to the 0.16 tesla field. Comparison of micronuclei results from exposed groups to those for control groups that were scored concurrently showed that there was no significant difference in frequency for either clone or either field intensity (P values in contingency table analyses were between 0.42 and 0.6); similarly, pink mutation frequencies for clone 4430 exposed and control groups did not differ significantly (a contingency test yielded χ2= 1.4 and P = 0.26). Comparisons of pink mutation frequencies during the first 6 days of clone 02 exposure to those in the period when an effect should be greatest (days 7 through 17 revealed no significant difference (χ2= 2.6 and P = 0.1) between the two scoring periods, through frequencies were higher during the early scoring p

ISSN:0192-2521    

DOI:10.1002/em.2860060107

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

年代:1984

数据来源: WILEY

摘要:

AbstractA number of metal compounds have been shown to be human carcinogens. Others, while not proven human carcinogens, are able to cause tumors in laboratory animals. Short‐term bacterial assays for genotoxic effects have not been successful in predicting the carcinogenicity of metal compounds. We report here the ability of some metal compounds to cause the induction of λ prophage inE coliWP2S(λ). By far the strongest inducing ability was observed with K2CrO4, followed by Pb(N03)2>MnCl2>Ni(OOCCH3)2>CrCl2>NaWO4>Na2MoO4>KMnO4. With the exception of chromate, long‐term exposures in a narrow, subtoxic dose range were required in order to demonstrate phage induction. A new microtiter assay for λ prophage induction, which incorporates these features, is described. This system also was able to detect very small amounts of organic carci

ISSN:0192-2521    

DOI:10.1002/em.2860060108

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

年代:1984

数据来源: WILEY

摘要:

AbstractMethyl chloroform (1,1,1‐trichloroethane) was identified as a major component in two fabric‐protector spray products. Mutagenic effects were determined at several dosage levels for the two products and some of the identified components. Levels of organics in the air of sealed desiccators, used as exposure chambers in modified Salmonella reversion assays, were measured by a gas chromatographic technique. Both fabric protectors and two samples of trichloroethane were mutagenic in strain TA 1535 and one of each was mutagenic in strain TA 100. Other constituents, such as petroleum distillate and p‐dioxane, were nonmutagenic at the tested exposure l

ISSN:0192-2521    

DOI:10.1002/em.2860060109

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

年代:1984

数据来源: WILEY

摘要:

AbstractThe failure of the C3H/10T1/2 cell transformation system to respond to numerous known carcinogens has limited its applications for the detection and study of cancer‐causing substances. Recent studies have found, however, that some carcinogens function as initiating agents for the process of transformation in these cells. Treatment with such agents is generally not sufficient to transform low‐density asynchronous cultures of C3H/101/2 cells, but morphologic transformation will occur if such cultures are subsequently exposed to the potent tumor promoter 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA). In the present study, the ability of TPA to enhance transformation was examined in cultures treated with a variety of chemical agents. The addition of TPA after chemical treatment enhanced the transformation of these cells by methylmethanesulfonate, ethylmethanesulfonate,N‐methyl‐N′‐nitro‐N‐nitrosoguanidine,N‐nitrosomethylurea,N‐nitrosoethylurea, mitomycin C, 5‐fluorodeoxyuridine, and 5‐azacytidine. Treatment with amethopterin or benzo(e)pyrene did not produce significant numbers of foci in the presence or absence of TPA. TPA inhibited transformation by high concentrations of 3‐methylcholanthrene and benzo(a)pyrene. Thus, numerous carcinogens function as initiating agents for these cells and the presence of TPA can dramatically increase the sensitivity o

ISSN:0192-2521    

DOI:10.1002/em.2860060110

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

年代:1984

数据来源: WILEY

摘要:

AbstractOrganic extracts of emissions from wood combustion have been fractionated by high performance liquid chromatography (HPLC) into 25–28 fractions. Each fraction was tested for mutagenic activity in a modified AmesSalmonella/microsome bioassay requiring one‐third of the test volumes needed for the ususal test. Direct mutagenic activity was noted predominantly in the most polar fractions, whereas indirect mutagenic activity was associated with the fractions containing polycyclic aromatic hydrocarbons (PAH) and with polar fractions probably consisting of aza‐arenes and aromatic a

ISSN:0192-2521    

DOI:10.1002/em.2860060111

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

年代:1984

数据来源: WILEY