DNA ADDUCT FORMATION IN PRIMARY MOUSE EMBRYO CELLS INDUCED BY 7H-DIBENZO[C,G]CARBAZOLE AND ITS ORGAN-SPECIFIC CARCINOGENIC DERIVATIVES

The nuclease P1 modification of the P-32-postlabeling technique was us ed to study the biological activity of 7H-dibenzo[c,g]carbazole (DBC) and some of ifs derivatives, including N-methyldibenzo[c,g]carbazole ( N-MeDBC), 5,9-dimethyldibenzo[c,g]carbazole (5,9-diMeDBC), 5,9,N-trime thyldibenzo[c,g]carbazole (5,9, N-triMeDBC), 6-methoxydibenzo[c,g]carb azole (6-McODBC), N-acetyldibenzo[c,g]carbazole (N-AcDBC), N-hydroxyme thyldibenzo[c,g]carbazole (N-HMeDBC) in primary mouse embryo cells. a very good correlation was round between carcinogenic specificity in vi vo of these N-heterocyclic aromatic hydrocarbons and their DNA-adducti on in vitro. Primary mouse embryo cells were able to metabolize and de tect tissue-specific sarcomagens N-MeDBC and 6-MeODBC as well as deriv atives with both sarcomagenic and hepatocarcinogenic activity, DEC, N- AcDBC, and N-HMeDBC. The strong specific hepatocarcinogen 5,9-diMeDBC in vivo, did not induce any DNA-adducts in the embryo cells, which sug gests that the enzymatic composition of the target tissue probably is the determining factor in the organ specificity of this derivative. 5, 9,N-triMeDBC, derivative without any carcinogenic activity in vivo, di d not induce any DNA-adducts in primary mouse embryo cells. Pretreatme nt of: cells with 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD) apparent ly stimulated DNA-adduct formation in the cells exposed to DEC, 6-MeOD BC, and N-MeDBC. No or a very slight effect of TCDD on DNA-adduct form ation was found in cells exposed to N-HMeDBC and N-AcDBC. Preliminary results have shown that TCDD slightly induced cytochrome P4501A1-linke d ethoxyresorufin O-deethylase (EROD) activity in primary mouse embryo cells. These data suggest the role of cytochrome P4501A1 in the metab olism of DBC derivatives with sarcomagenic activity. (C) 1997 Wiley-Li ss, Inc.