Induction of aryl hydrocarbon hydroxylase and DNA adduct formation in parental and carcinogen transformed C3H/10T1/2 clone 8 cells by benzo[a]pyrene.
C3H/10T1/2 clone 8 (10T1/2) cells possess aryl hydrocarbon hydroxylase (AHH) activity capable of metabolizing polycyclic aromatic hydrocarbons to ultimate carcinogenic forms. AHH activity in 10T1/2 cells was measured before and after culturing in the presence of benzo[a]pyrene (B[a]P), and compared to the AHH activity found in carcinogen-transformed 10T1/2 cell lines treated similarly. The cell lines were also examined for B[a]P-DNA adduct formation, using the 32P-postlabelling technique. Treatment of parental 10T1/2 cells with B[a]P was found to significantly increase AHH activity and produce substantial numbers of DNA adducts. In addition to a major B[a]P-DNA adduct, 5-6 minor DNA adducts were also detected. Relative to parental 10T1/2 cells, an aflatoxin B1-transformed 10T1/2 cell line (7SA) was found to have significantly depressed AHH activity. In addition, after treatment with B[a]P, 7SA cells had only 8% of the B[a]P-DNA adduct levels found in 10T1/2 cells. This system may provide an in vitro model for investigating mechanisms responsible for the depression of cytochrome P-450 activities by chemical carcinogens.
Faletto
M B
MB
Grace Cancer Drug Center, Roswell Park Memorial Institute, Buffalo, New York 14263.
Maccubbin
A E
AE
Koser
P L
PL
Vangalio
J A
JA
Gurtoo
H L
HL
D016604:Aflatoxin B1; D000348:Aflatoxins; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D001564:Benzo(a)pyrene / Q000096:biosynthesis* / Q000494:pharmacology*; D002460:Cell Line; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced; D002999:Clone Cells; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology; D004247:DNA / Q000096:biosynthesis*; D018736:DNA Adducts; D004790:Enzyme Induction; D005347:Fibroblasts / Q000166:cytology; D008297:Male; D051379:Mice; D010761:Phosphorus Radioisotopes; D051381:Rats; D011919:Rats, Inbred Strains
D000348:Aflatoxins; D018736:DNA Adducts; D010761:Phosphorus Radioisotopes; C056612:benzo(a)pyrene-DNA adduct; D001564:Benzo(a)pyrene; D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D016604:Aflatoxin B1; D001189:Aryl Hydrocarbon Hydroxylases