Tissue‐specific differences in adduct formation by hepatocarcinogenic and sarcomatogenic derivatives of 7H‐dibenzo[c,g]carbazole in mouse parenchymal and nonparenchymal liver cells

Abstract

Parenchymal (PC) and nonparenchymal (NPC) liver cells have different tissue-specific, procarcinogen activation enzymes. NPC appear to be protected against the mutagenic effects of lipotropic bulky adducts induced by carcinogens by a unknown mechanism. Most studies of activation have been conducted with whole liver. The purpose of this study was to differentiate adduct formation in mouse PC and in NPC, isolated after in vivo administration of 7H-dibenzo[c,g]carbazole (DBC), the most efficient liver carcinogen in mice, which also has potent sarcomagenic and epitheliomagenic activities. The very sensitive 32P-postlabeling method was used to detect adducts. Two tissue-specific DBC derivatives, 6-methoxy-DBC (6MeODBC), which is exclusively sarcomagenic, and 5,9-dimethyl-DBC (DiMeDBC), which is exclusively hepatocarcinogenic, were analyzed in parallel. Both PC and NPC generated the ultimate metabolites of DBC, but NPC were substantially less efficient. Clear-cut tissue-specific differences in adduct formation were established: the sarcomagenic 6MeODBC gave rise only to NPC-DNA adducts, and the hepatocarcinogenic DiMeDBC only to PC-DNA adducts. The chromatograms of the adducts were compared with those of mouse embryonic cells in culture and mouse epidermal cells. The results are discussed in connection with animal experiments with DBC, 6MeODBC, and dimethylbenzanthracene and with published data on PC and NPC activating enzymes. Environ. Mol. Mutagen. 29:346–356, 1997. © 1997 Wiley-Liss, Inc.