TISSUE-SPECIFIC DIFFERENCES IN ADDUCT FORMATION BY HEPATOCARCINOGENICAND SARCOMATOGENIC DERIVATIVES OF 7H-DIBENZO[C,G]CARBAZOLE IN MOUSE PARENCHYMAL AND NONPARENCHYMOL LIVER-CELLS
O. Perinroussel et al., TISSUE-SPECIFIC DIFFERENCES IN ADDUCT FORMATION BY HEPATOCARCINOGENICAND SARCOMATOGENIC DERIVATIVES OF 7H-DIBENZO[C,G]CARBAZOLE IN MOUSE PARENCHYMAL AND NONPARENCHYMOL LIVER-CELLS, Environmental and molecular mutagenesis, 29(4), 1997, pp. 346-356
Parenchymal (PC)and nonparenchymal(NPC) liver cells have different tis
sue-specific, procarcinogen activation enzymes. NPC appear to be prote
cted against the mutagenic effects of lipotropic bulky adducts induced
by carcinogens by a unknown mechanism. Most studies of activation hav
e been conducted with whole liver. The purpose of this stud was to dif
ferentiate adduct formation in mouse PC and in NPC, isolated after in
vivo administration of 7H-dibenzo[c,g]carbazole (DEC), the most effici
ent liver carcinogen in mice, which also has potent sarcomagenic and e
pitheliomagenic activities. The very sensitive P-32-postlabeling metho
d was used to detect adducts. Two tissue-specific DEC derivatives, 6-m
ethoxy-DBC (6MeODBC), which is exclusively sarcomagenic, and 5,9-dimet
hyl-DBC (DiMeDBC), which is exclusively hepatocarcinogenic, were analy
zed in parallel. Both PC and NPC generated the ultimate metabolites of
DEC, but NPC were substantially less efficient. Clear-cut tissue-spec
ific differences in adduct formation were established: the sarcomageni
c 6MeODBC gave rise only to NPC-DNA adducts, and the hepatocarcinogeni
c DiMeDBC only to PC-DNA adducts. The chromatograms of the adducts wer
e compared with those of mouse embryonic cells in culture and mouse ep
idermal cells. The results ore discussed in connection with animal exp
eriments with DEC, 6MeODBC, and dimethylbenzanthracene and with publis
hed data on PC and NPC activating enzymes. (C) 1997 Wiley-Liss, Inc.