摘要:

AbstractRat lymphocytes are a potentially useful and convenient cell system for monitoring the genotoxic effects of chemicals in vivo, but little is known about the ability of these cells to metabolize promutagens to genotoxic species. In this study, Fischer 344 rat lymphocytes were treated in vitro with benzo[a]pyrene (BaP), 2‐acetylaminofluorene (2‐AAF), and several of their metabolites, and DNA damage was measured using nucleoid sedimentation analysis. Of the BaP derivatives, BaP 4,5‐oxide and BaP 7,8‐diol‐9,10‐epoxide decreased lymphocyte nucleoid sedimentation, whereas BaP and BaP 7,8‐dihydrodiol had little effect. Among the 2‐AAF derivatives,N‐acetoxy‐2‐AAF,N‐hydroxy‐2‐AAF, andN‐hydroxy‐2‐aminofluorene damaged rat lymphocyte nucleoids, whereas 2‐AAF, 2‐aminofluorene, and fluorene produced little detectable damage. The decrease in nucleoid sedimentation produced byN‐hydroxy‐2‐AAF was not inhibited by paraoxon, salicylamide, or 2‐aminofluorene, whereas paraoxon inhibited damage produced byN‐acetoxy‐2‐AAF. In co‐culture assays, rat lymphocytes increased the mutagenicity ofN‐hydroxy‐2‐AAF inSalmonella typhimuriumstrain TA98, but mediated little or no mutagenic response with BaP, BaP 7,8‐dihydrodiol, and 2‐AAF. Also, human lymphocytes, but not rat lymphocytes, mediated a positive mutagenic response with BaP 7,8‐dihydrodiol in Chinese hamster ovary UV5 cells. Although rat lymphocytes may metabolize certain proximal genotoxic chemicals to DNA‐damaging species (e.g., N‐hydroxy‐2‐AAF), these data suggest that in vivo lymphocyte DNA damage is more likely to result from lymphocytes encountering reactive chemical derivatives produced by other cells. It is also clear that differences exist between the ability of human and rat lymphocytes to activate promutagens, and this may impact on th

ISSN:0270-3211    

DOI:10.1002/tcm.1770110202

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

年代:1991

数据来源: WILEY

摘要:

AbstractThe ability of polychlorinated biphenyls (PCBs) to induce chromosome aberrations and sister chromatid exchanges (SCE) in peripheral lymphocytes was studied in a group of workers occupationally exposed to PCBs during the production of the Czechoslovak PCB products Delor 103 and Delor 106. The effect of PCB exposure was compared between an exposed group (N = 32, 3.25 ± 0.34% aberrant cells, AB.C.), control group 1(N = 20, 1.30 ± 0.29% AB.C.), and control group 2 (N = 20, 1.60 ± 0.31% AB.C.). The length of PCB exposure over 10 yr increased the frequency of AB.C. in a group exposed for 11–15 yr to 3.40% (N = 5) and in a group exposed for 16–25 yr to 5.85% (N = 7) vs. an increase of 1.60% AB.C. in group C2and of SCE to 12.6 ± 0.9/cell vs. 6.9 ± 0.7 SCE/cell in C2. The clastogenic activity observed in this group may be the result of a high PCB concentration in blood plasma (320 ± 190 μg PCB/1), and it is probably related to its solubility in adipose tissue, when it may act as another mutagen and carcinogen biotransformati

ISSN:0270-3211    

DOI:10.1002/tcm.1770110203

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

年代:1991

数据来源: WILEY

摘要:

AbstractThe teratogenicity of cobalt chloride (CoCl2) was tested by the FETAX (Frog Embryo Teratogenesis Assay:Xenopus) procedure in the South African frog,Xenopus laevis.In five assays, beginning at 5 h post‐fertilization, groups ofXenopusembryos were incubated for 96 h in media that contained CoCl2at concentrations ranging from 1.8 × 10−6to 1.8 × 10−2mol/L; control groups were incubated in the same medium without added CoCl2. At 101 h post‐fertilization, surviving embryos were counted, fixed in formalin, and examined by microscopy to score malformations and measure head‐to‐tail lengths. In control embryos, survival was ≥95% and malformations were ≥5%. Malformations were found in>99% of embryos exposed to Co2 +levels ≥56 μmol/L. Co2 +‐exposed embryos showed a concentration‐related pattern of malformations, comprising gut malrotation, ocular anomalies, kinked tail, craniofacial dysplasia, cardiac deformities, and dermal blisters. Other concentration‐dependent abnormalities, not categorized as malformations, included stunted growth, edema, ventral distention, and hypopigmentation. Themedian embryolethal concentration(LC50) of CoCl2was 10.4 (SE ± 0.4) mmol/L; themedian teratogenic concentration(EC50) was 25 (SE ± 2) μmol/L; theteratogenic index(Tl = LC50/EC50) was 416 (SE ± 13), indicating that CoCl2is a pote

ISSN:0270-3211    

DOI:10.1002/tcm.1770110204

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

年代:1991

数据来源: WILEY

摘要:

AbstractSpecific antibodies and radioimmunoassay (RIA) were used to measure the levels of acetylated and deacetylated C‐8 substituted deoxyguanosine adducts in day 11 rat embryos and their associated yolk sacs after exposure of whole rat conceptuses in vitro to the teratogen N‐acetoxy‐2‐acetylaminofluorene (N‐Ac‐AAF). The deacetylated adduct predominates in both the embryo and the associated yolk sac, and a dose response for adduct formation was observed when adducts were quantitated by RIA. Immunohistochemical localization of the deacetylated adducts revealed that adducts were confined to the nuclei in all tissues examined and that the abundance of adducts varied within and between tissues. Our initial findings indicate that specific DNA adduct antibodies may be useful in the study of teratogenesis induced by a wide variety of agents that

ISSN:0270-3211    

DOI:10.1002/tcm.1770110205

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

年代:1991

数据来源: WILEY

摘要:

AbstractChlorohydroxyfuranones, by‐products of chlorine disinfection and drinking water contaminants, are shown to produce DNA strand breaks in human and rodent cells. One chlorohydroxyfuranone, 3‐chloro‐4‐dichloromethyl‐5‐hydroxy‐2[5H]‐furanone (MX), a potent bacterial mutagen, induces 232 ± 89 DNA strand breaks.(cell‐μM)−1in human CCRF‐CEM cells over a concentration range of 4.4 to 220 μM. This constitutes a DNA damage potency comparable to dimethylsulfate (DMS). By comparison, 3,4‐dichloro‐5‐hydroxy‐2[5H]‐furanone (MA), another chlorohydroxyfuranone which is approximately four orders of magnitude less mutagenic than MX inSalmonella typhimuriumstrain TA100 is only about tenfold less potent as an inducer of DNA strand breaks in these cells, i.e., 18.2 ± 3.1 strand breaks·(cell‐μM)±1. The DNA strand‐breaking potential of MX is inactivated by prior incubation with a rat liver S9 homogenate. In addition, both chlorohydroxyfuranones are ineffective at producing DNA strand breaks in primary rate hepatocytes (PRH) at concentrations below those which produce cytotoxicity as assessed by release of the cellular enzyme lactate dehydrogenase (LDH). Prior treatment of the PRH with μM diethyl maleate, a glutathione‐depleting agent, did not enhance the cytotoxicity nor the DNA strand‐breaking potential of either chlorohydroxyfuranone. This could indicate that glutathione‐glutathione‐S‐transferase is not an important mecha

ISSN:0270-3211    

DOI:10.1002/tcm.1770110206

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

年代:1991

数据来源: WILEY

ISSN:0270-3211    

DOI:10.1002/tcm.1770110201

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

年代:1991

数据来源: WILEY