ISSN:0192-2521    

DOI:10.1002/em.2860090302

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

年代:1987

数据来源: WILEY

摘要:

AbstractGroups of male B6C3F1 mice (N = 12) were exposed to ambient air or to gaseous 1,3‐butadiene (BD) at 6.25, 62.5, and 625 ppm for 10 exposure days (6 hr + T90/day). Exposure to BD induced in bone marrow: 1) a significant increase in the frequency of chromosomal aberrations (CA); 2) a significant elevation in the frequency of sister chromatid exchanges (SCE); 3) a significant lengthening of the average generation time (AGT); 4) a significant depression in the mitotic index (MI); and, as measured in the peripheral blood, 5) a significant increase in the proportion of circulating polychromatic erythrocytes (%PCE), and 6) a significant increase in the level of micronucleated PCE (MN‐PCE) and micronucleated normochromatic erythrocytes (MN‐NCE). The most sensitive indicator of genotoxic damage was the frequency of SCE (significant at 6.25 ppm), followed by MN‐PCE levels (significant at 62.5 ppm), and then by CA and MN‐NCE frequencies (significant at 625 ppm). The most sensitive measure of cytotoxic damage was AGT (significant at 62.5 ppm), followed by %PCE (significant at 625 ppm), and then by MI (significant by trend test only). Because each cytogenetic endpoint was evaluated in every animal, a correlation analysis was conducted to evaluate the degree of concordance among the various indicators of genotoxic and cytotoxic damage. The extent of concordance ranged from a very good correlation between the induction of MN‐PCE and the induction of SCE (correlation coefficient r = 0.9562) to the lack of a significant correlation between the depression in the MI and any other endpoi

ISSN:0192-2521    

DOI:10.1002/em.2860090303

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

年代:1987

数据来源: WILEY

摘要:

AbstractThe present study shows that the L‐arabinose resistance test inSalmonella typhimuriumdetects coffee as a strong mutagen in the absence of mammalian microsomal activation. The response of the Ara forward mutation assay was 8.5 times higher than that of TA104, which is the most sensitive to coffee of the tester strains of the Ames test. Both the mutagenesis protocol (preincubation test) and the additional genetic characteristics of the bacterial tester strain (excision repair deficiency, normal lipopolysaccharide barrier, and the presence of plasmid pKM101) were critical factors in the optimal induction by coffee of forward mutations to L‐arabinose resistance. All ten samples of roasted coffee analyzed with the Ara assay were highly mutagenic: one cup of coffee (150 ml) was calculated to induce 3‐4 × 106AraRmutants. In contrast, coffee prepared from unroasted beans (green coffee) had no mutagenic activity. Regular‐ and sugar‐roasted coffees showed similar mutagenicities, but the specific mutagenic activity of instant coffees (1559 AraRmutants/mg) was almost 2 times that of noninstant ones (834 AraRmutants/mg). The Ara assay allowed the direct testing of coffee, although it was demonstrated that lyophilization has no effect on the mutagenicity of this beverage. Like roasted coffee, roasted barley induced a large number of AraRmutants per mg (227), though its specific mutagenic activity was approximately 4 and 7 times lower than that of noninstant and instant coffees, re

ISSN:0192-2521    

DOI:10.1002/em.2860090304

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

年代:1987

数据来源: WILEY

摘要:

AbstractAcrylamide was tested without exogenous activation in L5178Y/TK+/−−3.7.2C cells for mutation at the thymidine kinase locus and for clastogenicity. Acrylamide gave a positive induced mutagenic response (approximately 70 mutants/106survivors) when tested at 600–650 μg/ml. The highest dose tested (850 μg/ml) resulted in an induced mutant frequency of approximately 380 mutants/106survivors (survival = 13%). Acrylamide induced almost exclusively small‐colony mutants, indicating that it might be acting by a clastogenic mechanism. As predicted, acrylamide was clastogenic, inducing both chromatid and chromosome breaks and rearrangements. A clearly positive clastogenic response was observed at both the 750 μg/ml and 850 μg/ml doses, which showed 16 and 64 aberrations per 100 cells, respectively (background = 3 aberrations per 100 cells). These studies indicate that the L5178Y/TK+/−mouse lymphoma assay can detect some chromosomal mutagens (clastogens) that show little activity in other single gene mutation assays, the CHO/HPRT

ISSN:0192-2521    

DOI:10.1002/em.2860090305

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

年代:1987

数据来源: WILEY

摘要:

Abstract5‐(4‐Nitrophenyl)‐2,4‐pentadien‐1‐al (NPPD; spy dust) was tested for mutagenicity inSalmonellaand for its ability to induce chromosome aberrations and sister chromatid exchanges (SCE) in cultured Chinese hamster ovary (CHO) cells and mouse bone marrow. Two metabolites of NPPD produced by the rat, 4‐nitrobenzoic acid (NBA) and 4‐nitrohippuric acid (NHA), were also tested inSalmonellaand CHO cells. NPPD was mutagenic inSalmonella, and induced low‐level increases in chromosome aberrations and SCE in bone marrow. It did not induce aberrations in CHO cells. NBA was positive inSalmonellaand CHO cells, while NHA was negative. The mutagenicity of NPPD inSalmonellawas partially, but not completely, eliminated in a strain lacking one of the bacteria

ISSN:0192-2521    

DOI:10.1002/em.2860090306

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

年代:1987

数据来源: WILEY

摘要:

AbstractThe effect of route of administration on induction of unscheduled DNA synthesis (UDS) in mouse germ cells in vivo was studied using two germ cell mutagens, methyl methanesulfonate (MMS) and triethylenemelamine (TEM). The chemicals were administered to male mice C3Hf × 101°F1by IP injection or gavage using acute or 5‐day subacute regimens. After completion of dosing, methyl‐[3H]thymidine ([3H]TdR) was injected into the testes, and spermatozoa were collected 16 days later. The sperm heads were isolated, and UDS was determined by the amount of [3H]TdR incorporated. Acute administration of MMS (2‐100 mg/kg) induced a strong, dose‐related UDS response. The response was slightly higher with IP injection than with gavage. The UDS response after five daily doses of 50 mg MMS/kg was 20‐30% higher than that induced by a single IP or gavage dose. Acute administration of TEM (0.05‐4.0 mg/kg) by IP injection or gavage induced weak and variable responses. Retesting TEM using inbred C3Hf mice produced weak but exposure‐related responses with both acute IP and gavage treatments. There was a slight increase in UDS response with subacute IP injection but not with subacute gavage. Acute testicular injection of TEM produced a higher but more variable UDS response. The study showed that gavage, as well as IP injection, can be used for the administration of test chemicals and that the subacute 5‐day regimen induced a higher UDS response than the acute regimen. Furthermore, the testicular route may enhance the detection of

ISSN:0192-2521    

DOI:10.1002/em.2860090307

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

年代:1987

数据来源: WILEY

摘要:

Abstractα,β‐Unsaturated aldehydes are reactive compounds which are ubiquitous in the environment. This class of compounds has been tested for mutagenicity inSalmonella typhimuriumby a number of groups who have obtained differing results. The present studies were undertaken to test the mutagenicity and toxicity of two novel α,β‐unsaturated aldehydes, specifically trans,trans‐muconaldehyde and trans‐4‐hydroxynonenal, and to re‐examine the mutagenicity of crotonaldehyde. Trans,trans‐muconaldehyde is a newly found microsomal metabolite of benzene, and trans‐4‐hydroxynonenal is a toxic aldehyde formed endogenously during lipid peroxidation. Compounds were tested inS. typhimuriumstrain TA 100 using a 30‐min liquid preincubation procedure. The present mutagenicity studies indicate that these α,β‐unsaturated aldehydes at first appear to be mutagenic, although only at concentrations which decrease survival counts, and result in a disappearance of the bacterial lawn. The colonies observed on mutagenicity test plates are not mutants but

ISSN:0192-2521    

DOI:10.1002/em.2860090308

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

年代:1987

数据来源: WILEY

摘要:

AbstractThe fungicide, captan, is known to induce point mutations in vitro. In extremely high doses, technical grade captan leads to duodenal tumors in mice. In short‐term in vivo assays for genotoxicity, equivocal results have been obtained with captan. In this study, the genotoxicity of captan was studied in vivo in the proximal small intestine of the mouse, the site of its oncogenicity. Orally administered captan up to 4,000 mg/kg body weight failed to induce a response in the small intestine nuclear aberration assay in a wide range of doses under a variety of experimental conditions, including pretreatment of animals with L‐buthionine‐S, R‐sulfoximine (an inhibitor of glutathione biosynthesis). 1,2,3,6‐Tetrahydrophthalimide and bis (trichloromethyl)disulfide, two compounds that have been identified as impurities in technical grade captan, also failed to produce positive results in t

ISSN:0192-2521    

DOI:10.1002/em.2860090309

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

年代:1987

数据来源: WILEY

摘要:

AbstractComplex hydrocarbon mixtures have proven difficult to evaluate in in vitro mutagenicity assays owing to their insolubility in aqueous environments. Pluronic® Polyol F127 (BASF Wyandotte, Parsippany, NJ), prepared as a 50% (w/w) solution in absolute ethanol, proved effective in emulsifying various petroleum hydrocarbon fractions. Its effectiveness in theSalmonella/microsomal assay was evaluated using model solutions each comprising a polycyclic aromatic hydrocarbon (PAH) dissolved in mineral oil. The PAHs used were benzo(a)pyrene, 3‐methylcholanthrene, and 7,12‐dimethylbenzanthracene. Model solutions were evaluated neat and as emulsions with the Pluronic® F127 solution or Tween 80. Similar levels of each PAH were prepared in dimethyl sulfoxide (DMSO) for comparison. Cytotoxicity and mutagenesis were evaluated in the preincubation technique using strain TA97. Little or no cytotoxicity or mutagenesis was evident for model solutions tested neat. However, emulsification of these PAH‐laden mixtures with the Pluronic® F127 solution yielded cytotoxic and mutagenic responses similar to, or greater than, those observed for PAHs delivered in DMSO. Model mixtures emulsified with Tween 80 were less active. Study results demonstrate that Pluronic® F127, prepared as a 50% (w/w) solution in absolute ethanol, is an effective vehicle for evaluating the mutagenic potential of complex hydrocarbon mixtures containing PAHs in theSalmonella/microsomal assay. Since PAHs are a class of insoluble hydrocarbons, the results also suggest the potential usefulness of the Pluronic® F127 solution to detect the mutagenicity of other insoluble hydrocarbons and hydrocarbo

ISSN:0192-2521    

DOI:10.1002/em.2860090310

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

年代:1987

数据来源: WILEY

摘要:

AbstractThe frequency of thioguanine(TG)‐resistant lymphocytes in mice treated with ethylnitrosourea (ENU) was followed for a period of 51 wk using our clonogenic assay [Jones et al, 1985a,b]. The effects of dose (0‐58 mg/kg), time since treatment (2‐51 wk), dose rate (5 weekly × 11.7 mg/kg versus 1 × 58 mg/kg), and age at time of treatment (3 vs 15 mo) on the frequency of TG‐resistant, concanavalin A‐responsive spleen cells were evaluated. The frequencies of TG‐resistant spleen cells were generally dose responsive for 51 wk after exposure to ENU. They also were dependent upon the time that had elapsed since treatment with ENU, increasing to maximal values at 10 wk as previously reported [Jones et al, 1985a], and holding essentially stable at values of ∼20% of the maximum frequency from week 15 until at least week 40 for the 3‐month‐old mice. Fractionation of 58 mg ENU/kg into 5 weekly doses did not affect the frequency of ENU‐induced TG‐resistant cells detected in the spleen but did increase the rate of appearance in the spleen, and the efficiency of induction by the unit dose, of TG‐resistant cells. The mice exposed to ENU at 15 mo of age appeared to have a 4‐fold reduction in the rate of increase in frequency of ENU‐induced TG‐resistant spleen cells. One set of control mice was found to have a 10‐fold elevated frequency of TG‐resistant cells in both the spleen and thymus, indicating that mutations can occur

ISSN:0192-2521    

DOI:10.1002/em.2860090311

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

年代:1987

数据来源: WILEY