ISSN:0192-2521    

DOI:10.1002/em.2860020102

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

年代:1980

数据来源: WILEY

ISSN:0192-2521    

DOI:10.1002/em.2860020103

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

年代:1980

数据来源: WILEY

摘要:

AbstractSister chromatid exchange (SCE) techniques were used to analyze the genetic effects of ethyl carbamate (urethane) in cultured mouse‐bone marrow cells, and in several different mouse tissues in vivo. Ethyl carbamate concentrations up to 5.0 mg/ml were ineffective in causing a significant elevation of SCE in vitro. After in vivo drug administration, bone marrow, liver and spermatogonial cells all revealed significant dose‐related increases in SCE. Baseline and relative incremental levels of SCE were somatic vs germ tissue‐specific. Regenerating liver cells exhibited significantly greater absolute SCE values than all other tissues examined. Marrow cells revealed intermediate values, while germ cells were the least sensitive in SCE responsiveness. Spermatogonia required a fourfold higher dose, over that effective in somatic tissues, to promote an approximate doubling of the baseline SCE level.In vivo SCE analysis affords sensitive risk assessments for different tissues. Thus, this approach should be generally useful for studying compounds with questionable mutagenic potential, and/or those exerting target organ specificities of related biological activity (eg, toxicity, carcinogen

ISSN:0192-2521    

DOI:10.1002/em.2860020104

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

年代:1980

数据来源: WILEY

摘要:

AbstractCyclohexene oxide (CCHO) and 1,1,1‐trichloropropene‐2,3‐oxide (TCPO) are inhibitors of epoxide hydratase and have been used in studies of the mechanisms of mutagenesis in bacterial mutagenesis assays. The present studies were designed to investigate the mutagenic activity of CCHO and TCPO in Salmonella typhimurium employing the Ames histidine‐reversion assays (TA98, TA100, TA1535, TA1537, TA1538) and a forward mutation assay that uses 8‐azaguanine resistance in TM677 as the genetic marker. In the reverse mutation assay, TCPO (10−3M) produced a mutagenic response in strains TA100 and TA1535 in the absence or presence of a rat liver metabolizing system (S9), indicating that TCPO causes base‐pair substitution mutations. CCHO (10−3M) showed a slight but significant mutagenic effect in strain TA100, with or without S9 and, in strain TA1535, only in the absence of S9. In the forward assay, TCPO was a strong mutagen at concentrations above 5 × 10−5M and was toxic to the bacteria. The mutagenic and toxic effects of TCPO were slightly reduced in the presence of the S9 preparation, suggesting that the epoxide may be metabolized by the microsomal enzymes. In the forward assay, CCHO showed no mutagenic activity but some toxicity at 3 × 10−3M. When epoxide hydratase activity was measured under the conditions of the forward mutation assay, 85% inhibition of activity was observed at 10−3M TCPO, a concentration that caused a 45‐fold increase in the mutation frequency. CCHO (3 × 10−3M) produced a 55% inhibition of epoxide hydratase activity without exhibiting mutagenic effects in TM677. These results indicate that CCHO should be employed in preference to TCPO when inhibition of epoxide hydratase activity is required in b

ISSN:0192-2521    

DOI:10.1002/em.2860020105

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

年代:1980

数据来源: WILEY

摘要:

AbstractBromodeoxyuridine (BrdUrd) pellets weighing either 20, 25, 30, 35, 40, 45, or 53 mg were implanted subcutaneously in strain DBA/2J male mice. Femoral bone marrow cells were analyzed for sister chromatid exchange (SCE) and chromosome aberration frequencies, mitotic indices, and cellular replication kinetics. Small but statistically significant BrdUrd dose‐dependent increases of SCEs were observed, whereas chromosome aberrations were induced at low frequencies and occurred independently of BrdUrd dose. The mitotic index remained relatively constant for all doses. A slight inhibition of cellular replication, as manifested by a reduction in third division cells at the 40‐ and 45‐mg doses, was observed. The use of an intense fluorescent light source in the fluorescence‐plus‐Giemsa technique provided consistently good sister chromatid differentiation at pellet doses substantially lower than those previously used by other inve

ISSN:0192-2521    

DOI:10.1002/em.2860020106

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

年代:1980

数据来源: WILEY

摘要:

AbstractTwo routes of administration ‐ intraperitoneal injection and oral gavage ‐ and two methods of analysis ‐ direct metaphase preparations and the micronucleus test ‐ were used to investigate the cytogenetic effects of benzene exposure in the bone marrow of female and male Swiss (CD‐1) mice. The males demonstrated higher mean frequencies of metaphase aberrations and micronuclei after both routes of administration. The frequencies of metaphase aberrations appeared to be sex‐related and independent of the route of exposure, however, while the frequencies of micronuclei appeared to be dependent upon both the sex of the animals and the route of adm

ISSN:0192-2521    

DOI:10.1002/em.2860020107

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

年代:1980

数据来源: WILEY

摘要:

AbstractHormonal regulation of dimethylnitrosamine (DMN) metabolism by mouse kidney microsomes was investigated using an in vitro mutagenesis system that detects bioactive metabolites of this procarcinogen by measuring reverse mutation in Salmonella typhimurium his auxotrophs. Induction of microsomal DMN metabolizing enzymes was androgen‐specific. Testosterone and medroxyprogesterone acetate were active inducers, d/1 norgestrel was less active, while epitestosterone, estradiol, and progesterone were ineffective. The response to testosterone and medroxyprogesterone acetate was time‐ and dose‐dependent. Eleven strains of inbred mice were screened for their response to exogenous testosterone. DMN metabolism was stimulated in all mouse strains except for RF/J mice. Other androgenic end points were responsive in the latter strain, however.These observations suggest that induction of renal microsomal DMN metabolising enzymes is androgen‐specific and probably mediated via the androgen receptor. The insensitivity of RF/J mice may be due to a mutation affecting a key step in the enzymatic activation

ISSN:0192-2521    

DOI:10.1002/em.2860020108

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

年代:1980

数据来源: WILEY

摘要:

AbstractShort‐chain, 2‐ and 3‐carbon halogenated hydrocarbons were tested for mutagenicity for Salmonella typhimurium strain TA 100 both with and without the presence of S‐9. Without exception, all brominated derivatives were more mutagenic than the chlorinated derivatives, usually by a substantial order of magnitude. 2‐Fluoroethanol, the only fluorinated compound tested, showed little or no mutagenic activity up to 100 μmole per plate concentration. Two highly purified propane derivatives containing a halogen atom on each of the three carbons showed little or no direct mutagenic activity. A third trihalogenated compound with a halogen atom on each carbon atom showed some direct mutagenic activity, probably due to impurities. However, all three trihalogenated compounds were highly active mutagens following S‐9 activation. The presence of a double bond in the case of 1,2,3‐trichloropropene resulted in a higher level of direct mutagenic activity than 1,2,3‐trichloropropane, but activation with S‐9 resulted in a further increase in mutagenic activity with the former compound. On the other hand, S‐9 caused a substantial decrease in mutagenic activity of most compounds containing a double bond. With the presence of an alcoholic group in a compound, the addition of S‐9 caused variable responses, increasing the number of his+revertant colonies due to 2,3‐dibromopropanol but had little or no effect with five other compounds containing an alcoholic group. Evidence is also presented that the position of a double bond in relation to the halogen atoms may infl

ISSN:0192-2521    

DOI:10.1002/em.2860020109

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

年代:1980

数据来源: WILEY

摘要:

AbstractPublished reports have suggested the possible association of mutagenic or teratogenic properties of some benzimidazole analogs with induced spindle disruption and consequent mitotic arrest. Studies were conducted to explore this correlation. Seven benzimidazole analogs were evaluated in a human lymphocyte system for ability to block mitosis at metaphase. Confirming the previously reported results, four compounds, mebendazole, parbendazole, cambendazole, and fenbendazole, caused metaphase accumulation, which we found to be dose and time‐related. Minimum effective dose for mebendazole and cambendazole was 10 μg/ml; for parbendazole, 1 μg/ml; and for fenbendazole, 100 μ/ml. The drug‐induced mitotic arrest is qualitatively and quantitatively similar to that produced by colcemid. No activity was observed with three other compounds, benzimidazole, thiabendazole, and oxfendazole when tested at 100 μg/ml. Presence or absence of mitotic effects is correlated with reported teratogenicity with five out of the seven analogs. This suggests some utility of mitotic assessments for predicting teratog

ISSN:0192-2521    

DOI:10.1002/em.2860020110

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

年代:1980

数据来源: WILEY

摘要:

AbstractThis study was designed to examine suspended air particulates from the Houston atmosphere. Airborne particulates were collected using either a hi‐vol sampler (one stage from 0.01 to 25 μm) or an Anderson Cascade Impactor, the five stages of which roughly resemble the human respiratory tract. After organic extraction, the Ames assay was used to determine the mutagenic content of extracts, and the ability to induce prophage was assessed. Also DNA‐repair‐deficient cells were employed to see if the extracts caused DNA damage and what portion of the premutational lesions was repaired in normal cells.Results indicate that extracts of particulates from Houston air cause a significant number of mutations in bacteria and that the highest frequency of reversions is associated with the smallest particulates. An excision repair system is operative in bacteria which is able to assuage damage done to DNA by these extracts. The extracts did not cause prophage ind

ISSN:0192-2521    

DOI:10.1002/em.2860020111

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

年代:1980

数据来源: WILEY