Metabolic activation of benzo[a]pyrene in two fetal mouse hepatocyte lines: induction of DNA adducts and micronuclei.
We have studied the metabolic competence of two non-transformed epithelial-like cell lines derived from fetal mouse liver, C 6 and C 2.8, to activate the promutagen benzo[a]pyrene by measuring both the induction of DNA adducts through the nuclease P1-enhanced 32P-postlabeling assay and the formation of micronuclei. The pattern and level of DNA adducts detected in C 6 and C 2.8 cells treated with benzo[a]pyrene were compared with those obtained in human peripheral blood lymphocytes treated with the same compound and with [3H]anti-benzo[a]pyrene diolepoxide. In both the cell lines and in human lymphocytes we observed a consistent induction of distinct DNA adducts. In C 6 and C 2.8 cells, the most evident adduct showed a position similar to that of the main adduct induced by [3H]-anti-benzo[a]pyrene diolepoxide in human lymphocytes. In addition, benzo[a]pyrene caused a significant increase of micronucleated C 6 and C 2.8 cells, whereas the frequency of micronuclei did not increase in CHO cells treated, for comparison, in the same way.
Canova
S
S
Department of Biology, University of Padova, Italy.
Viezzer
C
C
Venier
P
P
Navazio
L
L
Revoltella
R
R
Celotti
L
L
D000818:Animals; D001345:Autoradiography; D001564:Benzo(a)pyrene / Q000378:metabolism* / Q000633:toxicity*; D001711:Biotransformation; D016466:CHO Cells; D002460:Cell Line; D002855:Chromatography, Thin Layer; D006224:Cricetinae; D018736:DNA Adducts; D004101:Dihydroxydihydrobenzopyrenes / Q000633:toxicity*; D006801:Humans; D008099:Liver; D008214:Lymphocytes / Q000187:drug effects; D051379:Mice; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects*; D008938:Mitosis / Q000187:drug effects; D009153:Mutagens / Q000633:toxicity*; D010835:Phytohemagglutinins / Q000494:pharmacology; D015719:Single-Strand Specific DNA and RNA Endonucleases / Q000378:metabolism
D018736:DNA Adducts; D004101:Dihydroxydihydrobenzopyrenes; D009153:Mutagens; D010835:Phytohemagglutinins; D001564:Benzo(a)pyrene; D015719:Single-Strand Specific DNA and RNA Endonucleases