摘要:

AbstractThe fungicides thiram and ziram have been assayed in a battery of nine bacterial strains of different genetic specificity. The results obtained suggest the induction of excisable DNA lesion(s), and indicate similar mutability of strains with AT or GC base pairs at target sites. This mutagenic profile is clearly distinct from that of oxidative mutagens, and it does not support the proposed role of oxidative stress in the mechanism of dithiocarbamates mutagenicity in bacteria.Furthermore, the bone marrow micronucleus test has been carried out in B6C3F1 mice with intraperitoneal administration of high grade thiram (12.5–50 mg/kg) and ziram samples (2.5–10 mg/kg in males, and 5–20 mg/kg in females). Thiram produced a significant increase of micronucleated PCEs in male mice sampled 48 h after treatment with 25, 37.5, and 50 mg/kg. No significant increase was detected in treated females. Ziram, tested in a lower range of doses because of its higher toxicity, resulted negative in both sexes. Both the acute toxicity and the ratio polychromatic/normochromatic erythrocytes indicated some sex specificity in the toxic effects induced by these dithiocarbamates in the B6C3F1 mouse. © 1992 Wiley‐L

ISSN:0270-3211    

DOI:10.1002/tcm.1770120302

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

年代:1992

数据来源: WILEY

摘要:

AbstractGlutathione S‐transferase (GST) isozymes from human fetal liver (16–18 weeks gestation) were purified by affinity chromatography followed by ion‐exchange high performance liquid chromatography (HPLC). The purified isozymes were used to investigate toxicity of 1,2‐dibromoethane(EDB) in an in vitro model of rat embryos in culture as passive targets. At least five isozymes of GST were found in the human fetal liver. Two anionic forms [pI values 5.5 (P‐2) and 4.5 (P‐3)] and one basic form [pI value 8.7 (P‐6)]were clearly separated. The presence of two near‐neutral forms was also identified. All the isozymes of the human fetal liver GSTs tested metabolized EDB (specific activities were 2.1, 7.0, and 2.0 μmol of GSH consumed/min/mg protein for P‐2, P‐3, and P‐6 isozymes, respectively). Covalent binding of EDB to DNA and protein was 144% and 212% higher, respectively, with the P‐3 anionic isozyme when compared to the P‐6 basic isozyme of GST. No covalent binding to either protein or DNA was observed with the P‐2 isozyme.EDB bioactivation by the GST isozyme P‐3 (15 units; 1 unit = 1 nmol of GSH consumed/min) resulted in toxicity to cultured rat embryos. Significant reductions of crown rump length, yolk sac diameter, and the composite score of morphological parameters (Brown and Fabro method) were observed. The central nervous system, optic and olfactory systems, and the hind limb were most significantly affected. The results of this investigation suggest that EDB may be classified as a suspected developmental toxicant in

ISSN:0270-3211    

DOI:10.1002/tcm.1770120303

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

年代:1992

数据来源: WILEY

摘要:

AbstractExposure of N‐nitrosodiethylamine (NDEA) to hermaphroditic fish (Rivulus marmoratus) embryos induced specific congenital malformations when the chemical was applied to embryos on days 0–6 post morula stage. This sensitive period generally coincided with the known period of organogenesis in this species, and the incidence of anomalies was clearly dose related. These results indicate that NDEA is teratogenic to fish embryos. © 1992 Wiley‐Lis

ISSN:0270-3211    

DOI:10.1002/tcm.1770120304

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

年代:1992

数据来源: WILEY

摘要:

AbstractN‐methyl‐N‐nitrosourea (MNU) and N‐ethyl‐N‐nitrosourea (ENU) are gestational stage dependent teratogens and transplacental carcinogens capable of inducing neurogenic tumours in rats. Intravenous treatment of gravid Wistar rats showed that MNU is teratogenic but ENU is a transplacental carcinogen and may be a teratogen when administered on day 12 of gestation. Twenty‐four hours after single doses of 2, 5, or 10 mg MNU/kg on day 12, dose dependent decreases in embryonic wet weight and total embryonic DNA were observed. Rats similarly treated with 2 and 5 mg MNU/kg showed dose dependent decreases in fetal brain DNA synthesis, DNA content, and wet weight 9 days later. Administration of single ENU doses of 1.5, 3, 6, 12, 48, and 80 mg/kg to day 12 embryos resulted in a dose dependent reduction in [methyl‐14C]‐thymidine (14C‐TdR) incorporation into DNA after 24 h although total DNA amounts and embryonic wet weights were unaffected.Benzoylated DEAE‐cellulose (BD‐cellulose) chromatography fractionates DNA on the basis of secondary structure by stepwise elution of double‐stranded DNA with 1.0 M NaCl solution (SE‐DNA) followed by elution of DNA containing single‐stranded regions with caffeine solution (CE‐DNA). Day 13 embryonic and day 21 fetal brain DNA was monitored by in vivo labelling with [methyl‐3H]‐thymidine on days 6 and 7 of gestation. Significant reduction in percentages of CE‐DNA (%CE‐DNA) 24 h after treatment of day 12 embryos with 2, 5, or 10 mg MNU/kg were attributed to the necrotic effect of MNU. Day 12 treatment with MNU produced no change in %CE‐DNA values of day 21 fetal brains. A teratogenic dose of 80 mg ENU/kg to day 12 embryos resulted in significantly increased %CE‐DNA values compared to controls but no changes were observed after 1.5 to 48 mg/kg. Analysis of the distribution of %CE‐DNA values from the 80 mg ENU/kg treated litter showed that the increase in %CE‐DNA was due to a second distinct population of embryos with higher %CE‐DNA values than controls.Incorporation of14C‐TdR into embryonic and fetal brain DNA demonstrated the effects of treatment with these compounds on DNA synthesis in vivo. The relative %CE‐DNA is expressed as the ratio of the percentage of caffeine‐eluted14C‐labelled DNA to %CE‐DNA (i.e., %CE‐14C‐DNA:%CE‐3H‐DNA). In the majority of control embryos the14C‐specific activity of CE‐DNA was higher than the14C‐specific activity of SE‐DNA. Treatment with ENU doses between 1.5 and 48 mg/kg on day 12 of gestation resulted in a dose dependent increase in the percentage of embryos from each litter with higher conentrations of newly synthesized DNA in SE‐DNA than in CE‐DNA.The results of this study suggest that mechanisms of ENU induced teratogenesis and transplacental carcinogenesis may be different although alkylation of embryonic DNA may initiate both phenomena. BD‐cellulose fractionation of embryonic DNA showed differences in the DNA secondary structural changes produced by MNU and ENU, suggesting they may not share the same mechanism of teratogenisis. The pertinence of relative %

ISSN:0270-3211    

DOI:10.1002/tcm.1770120305

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

年代:1992

数据来源: WILEY

ISSN:0270-3211    

DOI:10.1002/tcm.1770120301

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

年代:1992

数据来源: WILEY