On the bioactivation and genotoxic action of fluoranthene.
Fluoranthene (FA) was studied with respect to possible mechanisms of its high mutagenicity but low carcinogenicity, in comparison with the corresponding properties of benzo[a]pyrene (BaP), and with regard to the synergism of these two compounds shown by van Duuren and Goldschmidt (J Natl Cancer Inst 56, 1976, 1237). FA and BaP activated by S9 from Aroclor 1254 (PCB)-treated rats induce HPRT mutations in CHO cells with about equal effectiveness at the same exposure doses, which also lead to the same frequencies of repairable DNA adducts, enzyme-induced strand breaks being used as an indirect measure of adducts to DNA. FA was also shown to be an efficient inducer of SCE in human peripheral lymphocytes cocultivated with PCB-treated HepG2 cells or with liver cells from PCB-pretreated rats. For the induction of SCE, FA and BaP were shown to act additively. From metabolic studies with liver microsomes from C57Bl/6 mice it is concluded that, whereas BaP induces the metabolism of BaP to the mutagenic epoxide, neither BaP nor FA is able to induce the metabolism of FA. In mutation experiments with V79 cells (XEM2) constitutive for P450 IA1 activity, BaP 7,8-diol but not FA 2,3-diol provokes a high frequency of HPRT mutations. In cells constitutive for P450 IA2 enzymatic activity FA and BaP are but weakly mutagenic and practically nonmutagenic, respectively. Due to the additivity of the genotoxic effects of FA and BaP, induction of an error-prone condition by the latter compound seems to be excluded.(ABSTRACT TRUNCATED AT 250 WORDS)
Vaca
C
C
Department of Radiology, Stockholm University, Sweden.
Törnqvist
M
M
Rannug
U
U
Lindahl-Kiessling
K
K
Ahnström
G
G
Ehrenberg
L
L
D000818:Animals; D001140:Aroclors / Q000633:toxicity; D001564:Benzo(a)pyrene / Q000378:metabolism / Q000633:toxicity; D002273:Carcinogens; D020111:Chlorodiphenyl (54% Chlorine); D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D005449:Fluorenes / Q000378:metabolism* / Q000633:toxicity*; D006801:Humans; D066298:In Vitro Techniques; D007274:Injections, Intraperitoneal; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D009154:Mutation; D010088:Oxidoreductases / Q000032:analysis; D010105:Oxygenases / Q000378:metabolism; D012854:Sister Chromatid Exchange
D001140:Aroclors; D002273:Carcinogens; D005449:Fluorenes; D020111:Chlorodiphenyl (54% Chlorine); D001564:Benzo(a)pyrene; C007738:fluoranthene; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D010105:Oxygenases; D019363:Cytochrome P-450 CYP1A1