摘要:

Abstract1,2‐Diethylhydrazine (DEH) and dimethylnitrosamine (DMN) are indirect acting carcinogens that require metabolic activation to exert their potency. DEH is a transplacental carcinogen and teratogen in Wistar rats when administered by i.p. injection on day 12 of gestation. DMN is embryotoxic during this period. In this study, gravid Wistar rats were injected i.v. with DEH (10, 15, or 20 mg/kg) or i.p. with DMN (10 or 30 mg/kg) and the effects on the embryos 24 hours later were observed. Controls were similarly injected with saline vehicle. The incidence of resorptions increased after treatment with 20 mg DEH/kg. DEH treatment also resulted in decreases in embryo wet weights and total DNA that were not dose dependent. Treatment with DMN did not affect embryonic wet weights and total embryonic DNA amount when compared to the saline‐treated controls. The effects of DEH and DMN on DNA synthesis in vivo were monitored by injecting [methyl‐14C]‐thymidine 1 hour prior to embryo death. DEH induced significant increases in thymidine incorporation into embryo DNA but the increases were not proportional to the doses administered. DNA synthesis was significantly decreased in embryos treated with 30 mg DMN/kg. The DNA of treated and control embryos was fractionated by benzoylated DEAE‐cellulose (BD‐cellulose) chromatography to determine differences in DNA secondary structure following treatment. BD‐cellulose chromatography separates double‐stranded DNA from DNA containing single‐stranded regions by step elution with 1 M NaCl solution and caffeine solution, respectively. Embryonic DNA was monitored by in vivo labelling with [methyl‐3H]‐thymidine on days 6 and 7 of gestation. Significant dose dependent increases in percentages of caffeine‐eluted DNA (%CE‐DNA) compared to controls were detected after treatment with 10, 15, and 20 mg DEH/kg and 10 and 30 mg DMN/kg. The relative %CE‐DNA is expressed as the ratio of %CE‐14C‐labelled DNA to %CE‐3H‐labelled DNA. Litters treated with 10, 15, and 20 mg DEH/kg had relative %CE‐DNA values significantly lower than controls. The results support the hypothesis that initiation mechanisms of transplacental carcinogenesis and teratogenesis are different. The pertinence of %CE‐DNA and relative %CE‐DNA values to the study of transplacental carcinogenesis and teratogen

ISSN:0270-3211    

DOI:10.1002/tcm.1770140202

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

年代:1994

数据来源: WILEY

摘要:

AbstractIn previous studies using methylating agents a correlation was found between the initial DNA adduct rate (O6‐methylguanine) in the embryo and the teratogenic efficiency. This was shown by measuring DNA adduct rates in the teratogenic dose range which exhibited similar adduct rates at the equivalent teratogenic dose levels.A similar approach was performed using the ethylating agent ethylmethanesulfonate (EMS). In the teratogenic dose range (150–250 mg/kg bw) the adduct rates of O6‐ethylguanine were similar compared to those of O6‐methylguanine which were obtained with methylating agents. We conclude that a correlation between teratogenicity and adduct rate (O6‐alkylguanine) exists for both methylating and ethylating agents.Furthermore, DNA adduct formation following doses at and below the no‐observed‐adverse‐effect‐level (NOAEL) of teratogenicity was determined. The lowest experimental dose was 45 mg/kg EMS. Substantial DNA adduct rates in the embryos were found. These data will be used for molecular dosimetry in a risk assessment of low doses. © 19

ISSN:0270-3211    

DOI:10.1002/tcm.1770140203

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

年代:1994

数据来源: WILEY

摘要:

AbstractChlorophyllin, a derivative of chlorophyll, is known to be an antimutagenic agent. Studies were performed to determine whether chlorophyllin can also inhibit morphological transformation of BALB/3T3 cells induced by carcinogens and complex mixtures. Chlorophyllin was added to the cultures simultaneously with carcinogens or complex mixtures while the transformation assay was conducted. At concentrations that did not significantly affect cell growth, chlorophyllin was found to inhibit morphological transformation induced by N‐methyl‐N′‐nitro‐N‐nitrosoguanidine, 3‐methylcholanthrene, 7,12‐dimethylbenz(a)anthracene, benzo(a)pyrene, aflatoxin B1, and extracts of coal dust, tobacco snuff, and chewing tobacco. In all cases, the mean number of transformed foci per flask treated with chlorophyllin was significantly lower than that of untreated cultures. The reduction in the number of transformed foci was dependent on the concentration of chlorophyllin tested. These results indicate that chlorophyllin is an antitransforming agent. © 1994

ISSN:0270-3211    

DOI:10.1002/tcm.1770140204

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

年代:1994

数据来源: WILEY

摘要:

AbstractTwenty‐one chemicals carcinogenic in rodent bioassays were selected for study. The chemicals were administered by gavage in two dose levels to female Sprague‐Dawley rats. The effects of these 21 chemicals on four biochemical assays [hepatic DNA damage by alkaline elution (DD), hepatic ornithine decarboxylase activity (ODC), serum alanine aminotransferase activity (ALT), and hepatic cytochrome P‐450 content (P450)] were determined.Available data from seven cancer predictors published by others [the Ames test (AMES), mutation inSalmonella typhimuriumTA 1537 (TA 1537), structural alerts (SA), mutation in mouse lymphoma cells (MOLY), chromosomal aberrations in Chinese hamster ovary cells (ABS), sister chromatid exchange in hamster ovary cells (SCE), and the ketest (ke)] were also compiled for these 21 chemical carcinogens plus 28 carcinogens and 62 noncarcinogens already published by our laboratory. From the resulting 111 (chemicals) by 11 (individual cancer predictors) data matrix, the five operational characteristics (sensitivity, specificity, positive predictivity, negative predictivity, and concordance) of each of the 11 individual cancer predictors (four biochemical parameters of this study and seven cancer predictors of others) are presented.Two examples of complementarity or synergy of composite cancer predictors were found. To obtain maximum concordance it was necessary to combine both genotoxic and nongenotoxic cancer predictors. The composite cancer predictor (DD or [ODC and P450] or [ODC and ALT]) had higher concordance than did any of the four individual cancer predictors from which it was constructed. Similarly, the composite cancer predictor (TA 1537 or DD or [ODC and P450] or [ODC and ALT]) had higher concordance than any of its five individual constituent cancer predictors. Complementarity or synergy has been demonstrated both (1) among genotoxic cancer predictors (DD and TA 1537) and (2) between nongenotoxic (ODC, P450, and ALT) and genotoxic cancer predictors (TA 1537 and DD). ©1993 Wiley‐Liss, Inc.This article is a US Government work and, as suh, is in the public domain in the United States of

ISSN:0270-3211    

DOI:10.1002/tcm.1770140205

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

年代:1994

数据来源: WILEY

ISSN:0270-3211    

DOI:10.1002/tcm.1770140206

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

年代:1994

数据来源: WILEY

ISSN:0270-3211    

DOI:10.1002/tcm.1770140207

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

年代:1994

数据来源: WILEY

ISSN:0270-3211    

DOI:10.1002/tcm.1770140201

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

年代:1994

数据来源: WILEY