Parenchymal (PC) and nonparenchymal (NPC) liver which is exclusively hepatocarcinogenic, were anacells have different tissue-specific, procarcinogen lyzed in parallel. Both PC and NPC generated the activation enzymes. NPC appear to be protected ultimate metabolites of DBC, but NPC were substanagains
DNA adduct formation in primary mouse embryo cells induced by 7H-dibenzo[c,g]carbazole and its organ-specific carcinogenic derivatives
✍ Scribed by A. Gábelová; O. Périn-Roussel; Y. Jounaidi; F. Périn
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- English
- Weight
- 157 KB
- Volume
- 30
- Category
- Article
- ISSN
- 0893-6692
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✦ Synopsis
The nuclease P1 modification of the 32 P-postlabeling DNA-adducts in the embryo cells, which suggests that technique was used to study the biological activity the enzymatic composition of the target tissue probaof 7H-dibenzo[c,g]carbazole (DBC) and some of its bly is the determining factor in the organ specificity of derivatives, including N-methyldibenzo[c,g]carbazole this derivative. 5,9,N-triMeDBC, derivative without (N-MeDBC), 5,9-dimethyldibenzo[c,g]carbazole (5,9-any carcinogenic activity in vivo, did not induce any diMeDBC), 5,9,N-trimethyldibenzo[c,g]carbazole DNA-adducts in primary mouse embryo cells. Pretreat-(5,9,N-triMeDBC), 6-methoxydibenzo[c,g]carbazole ment of cells with 2,3,7,8-tetrachlorodibenzo-p-dioxin (6-McODBC), N-acetyldibenzo[c,g]carbazole (N-(TCDD) apparently stimulated DNA-adduct forma-AcDBC), N-hydroxymethyldibenzo[c,g]carbazole (N-tion in the cells exposed to DBC, 6-MeODBC, and HMeDBC) in primary mouse embryo cells. A very N-MeDBC. No or a very slight effect of TCDD on good correlation was found between carcinogenic DNA-adduct formation was found in cells exposed specificity in vivo of these N-heterocyclic aromatic hy-to N-HMeDBC and N-AcDBC. Preliminary results drocarbons and their DNA-adduction in vitro. Primary have shown that TCDD slightly induced cytochrome mouse embryo cells were able to metabolize and de-P4501A1-linked ethoxyresorufin O-deethylase (EROD) tect tissue-specific sarcomagens N-MeDBC and 6-activity in primary mouse embryo cells. These data MeODBC as well as derivatives with both sarco-suggest the role of cytochrome P4501A1 in the memagenic and hepatocarcinogenic activity, DBC, N-tabolism of DBC derivatives with sarcomagenic AcDBC, and N-HMeDBC. The strong specific hepato-activity.
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