摘要:

AbstractBased on the findings of Nagao et al [1978] that phenacetin is negative in the standard Ames test with Aroclor induced rat S‐9 and positive with hamster S‐9, the test was performed with a mixture of rat/hamster S‐9. Phenacetin was mutagenic with the mixture. The activity of the mixture was compared to the rat S‐9 alone with low concentrations of 2‐aminoanthracene (a strong promutagen for Salmonella typhimurium TA 1535, TA 100, TA 1537, and TA 98), nitrosopiperidine (a weak promutagen), and 1, 2 epoxybutane (a weak, directacting mutagen). Except for an increased mutagenic activation by the mixture with nitrosopiperidine the mixture was comparable to the rat S‐9 alone, indicating that replacing rat S‐9 with a rat/hamster S‐9 mixture in the standard Ames test could increase the sensitivity of the test without interfering with r

ISSN:0192-2521    

DOI:10.1002/em.2860030102

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

年代:1981

数据来源: WILEY

摘要:

AbstractThe autoradiographic identification of unscheduled DNA synthesis (UDS) in primary cultures of adult rat hepatocytes (HPC) has been proposed as a predictive test for mutagens/carcinogens. To assess the predictive value of this test, results in the hepatocyte UDS assay were compared with data for bacterial mutagenicity using a modified Ames test. Over 200 compounds representing a variety of chemical classes consisting of procarcinogens, ultimate carcinogens, and noncarcinogens were tested in each system. The accurate discrimination of many carcinogens/noncarcinogens was demonstrated by both systems. The induction of UDS in hepatocytes showed an excellent correlation with bacterial mutagenesis in response to polycyclic aromatic hydrocarbons, aromatic amines, biphenyls, nitrosamines, carbamates, azo‐compounds, acridines, halogenated compounds, nitrosureas, quinolines, pyridines, purines, pyrimidines, esters and carbamates. Nitrocompounds, although active in bacteria, were poor inducers of UDS. The results support the complementary and confirmatory nature of these tests for genotoxic chemicals and indicate the usefulness of the hepatocyte UDS system as a component in a battery of short‐term predictive tests for mutagens/carcinog

ISSN:0192-2521    

DOI:10.1002/em.2860030103

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

年代:1981

数据来源: WILEY

摘要:

AbstractDialkylaminoalkyl chlorides, valuable chemical manufacturing intermediates, were evaluated for their mutagenicity in several short‐term assays: The concentration gradient bacterial mutagen assay, the Ames test, the L5178Y mouse lymphoma cell assay, and the hepatocyte primary culture‐DNA repair test. The dialkylaminoethyl chlorides were active in all test systems. The relative mutagenic potencies of the ethyl chlorides were similar in the bacterial tests and the L5178Y cell assay. The dialkylaminopropyl chlorides were weakly mutagenic in two Salmonella strains but were inactive in the other test systems.The purpose of the test battery used in these studies is to generate data on a test compound which could be used to make a rational prediction of the carcinogenic potential of the compound in test animals. On this basis, the results with the dialkylaminoethyl compounds suggest that if these agents which can form the aziridinium ion were evaluated in in vivo tests there is a reasonable chance some would be found to be carcinogenic. Alternatively, the data on the dialkylaminopropyl chlorides indicate that they have a rather low carcinogenic potent

ISSN:0192-2521    

DOI:10.1002/em.2860030104

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

年代:1981

数据来源: WILEY

摘要:

AbstractThe frequency of sister chromatid exchange (SCE) in WI‐38 cells was estimated by the 5‐bromodeoxyuridine (BrdUrd)‐dye technique after one hour's exposure to cyclophosphamide (CY), N‐methyl‐N′‐nitro‐N‐nitrosoguanidine (MNNG), 4‐nitroquinoline‐1‐oxide (4NQO), and maleic hydrazide (MH) with and without the addition of rat liver microsomal suspension (S‐9) fraction with co‐factors (S‐9 mix). CY at concentrations from 1 × 10−5M to 1 × 10−3M with S‐9 mix increased the number of SCEs per cell in a dose‐dependent manner. Without S‐9 mix, CY at concentrations below 1 × 10−3M failed to produce more SCEs than the controls. MNNG at 1 × 10−8M and 4NQO at 1 × 10−7M without S‐9 produced significant increases in SCEs per cell. Addition of S‐9 during treatment slightly decreased the effects of MNNG and 4NQO in the formation of SCEs. MH was tested at pH 6.4 and pH 7.6. At pH 7.6, MH at 1 × 10−3M without S‐9 mix inhibited cell multiplication, but did not cause a significant increase of SCEs per cell. There were no interactions between MH (2 × 10−4M) and S‐9 mix nor between MH and the pH levels tested. These results indicate that in the presence of metabolic activation, SCE formation in human diploid fibrob

ISSN:0192-2521    

DOI:10.1002/em.2860030105

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

年代:1981

数据来源: WILEY

摘要:

AbstractThrough a new approach, we have sought to isolate ultraviolet light (UV)‐sensitive and DNA repair mutant Chinese hamster fibroblasts. The procedure consisted of 1) mutation induction by 5‐bromodeoxyuridine (BrdU)‐blacklight and UV treatments; 2) incorporation of3H‐thymidine in repair‐proficient cells at high temperature (38.5°C) following UV damage; 3) cold holding (4.0°C) of these cells to induce tritium killing; and 4) recovery and testing of repair‐deficient and UV‐sensitive cells which have survived and formed colonies at low temperature (34.0°C). In our initial attempt at this protocol, we isolated 72 surviving colonies from 2 × 107cells plated for selection. Of the 72 colonies. 20 demonstrated potential interest and four were selected for extensive study. One, identified as UVs−7, is slightly more sensitive to UV, but not sensitive to X rays or N‐acetoxy‐2‐acetylaminofluorene (NAc‐AAF). The mutant exhibits a highly reduced level of unscheduled DNA synthesis (UDS), as compared to the parental line. Two additional lines, UVs−40 and UVs−44, are sensitive to UV, X ray, N‐methyl‐N‐nitro‐N‐nitrosoguanidine (MNNG), and NAc‐AAF, but exhibit normal UDS. A fourth line, UVr−23, has enhanced UDS, is resistant to UV, but exhibits no difference in sensitivity to X ray or NAc‐AAF. These mutants are all stable, and should be useful for the study of mammalian DNA

ISSN:0192-2521    

DOI:10.1002/em.2860030106

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

年代:1981

数据来源: WILEY

摘要:

AbstractSex‐linked recessive lethal mutations were induced in D melanogaster males by chronic as well as acute treatments of gaseous 1, 2‐dibromoethane ranging from 2.3 to 31 ppm.hr. Acute treatments corresponding to each chronic treatment were made by increasing chemical concentration approximately 30 times with a concomittant decrease in exposure period. Germ cell stages sampled, in order of decreasing sensitivity, were spermatocytes, spermatids, and spermatozoa. The most significant finding is that no consistent pattern of difference is observed between acute and chronic exposure for three of the four exposure levels. Only at the highest exposure level (30–31 ppm.hr) was any consistent difference observed between chronic and acute exposure levels. At the higher exposure level in all three germ cell stages the acute exposure showed a significant increase in mutation frequency over the chronic exposure. The greater acute vs chronic mutation frequency for spermatozoa, a metabolically inactive cell stage, leads to the conclusion that the exposure rate effect at high exposure levels is due to systemic factors such as metabolic deactivation or elimination rather than repair of premutational damage in the target cells. The significance of these observations in risk assessment for environmental pollutants is disc

ISSN:0192-2521    

DOI:10.1002/em.2860030107

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

年代:1981

数据来源: WILEY

摘要:

AbstractBefore exerting a carcinogenic or mutagenic effect, many carcinogens must undergo metabolic activation. Liver S‐9 preparations from rats treated with Aroclor 1254 (AC) have been widely used to extend the ability of the Salmonella mutagenicity assay to detect such nondirect‐acting agents. We compared the mutagen‐activating capabilities of liver S‐9 preparations from both Syrian golden hamsters and Sprague‐Dawley rats. The comparison was made between S‐9 fractions from untreated, and phenobarbital (PB)‐ and AC‐treated animals of both sexes. Also compared was the effect of varying the amount of S‐9 protein. The preparations from hamster liver were consistently more effective than preparations from rat liver for the activation of 2‐acetylaminofluorene (AAF), 2‐aminoanthracene (AA) (except for AC‐induced preparations), 3‐methylcholanthrene (MCA), and diethylnitrosamine (DEN) to their mutagenic forms. Induced preparations from rats were more active than those from hamsters when using benzo(a)pyrene (BP), while with uninduced preparations, the opposite was true.There was also a relationship between the amount of S‐9 protein and the number of revertant colonies obtained. With the aromatic amines (AAF and AA), a partial inhibition of mutagenicity occurred at the highest protein concentrations tested. With BP, an inverse relationship was observed between protein concentration and the number of revertants occurring in the presence of the preparation from PB‐ and AC‐induced male and female rats.The relative order of activities of aryl hydrocarbon hydroxylase (AHH) and BP‐4,5‐epoxide hydrase (EH) in

ISSN:0192-2521    

DOI:10.1002/em.2860030108

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

年代:1981

数据来源: WILEY

摘要:

AbstractUnstimulated lymphocytes from individuals with Down Syndrome (trisomy 21) are more sensitive to the induction of dicentric and ring aberrations by X rays than normal lymphocytes. Several explanations involving the more rapid rejoining of X‐ray–induced lesions in Down cells have been offered. It is shown here that the repair of the DNA damage converted into chromosome aberrations is more rapid in Down cells than normal cells. This more rapid repair results in a higher probability of producing chromosome aberrations, and hence higher aberration frequencies in Down than normal ce

ISSN:0192-2521    

DOI:10.1002/em.2860030109

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

年代:1981

数据来源: WILEY

ISSN:0192-2521    

DOI:10.1002/em.2860030110

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

年代:1981

数据来源: WILEY

ISSN:0192-2521    

DOI:10.1002/em.2860030111

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

年代:1981

数据来源: WILEY