A comparative study on the metabolic activation of 3,4-benzo[a]pyrene to mutagens by aorta smooth muscle cells of rat and rabbit.
The mutagenic activation of benzo[a]pyrene (BaP) after exposure to aorta smooth muscle cells of different origin was examined. Three test systems with different genetic endpoints--sister-chromatid exchange (SCE), gene mutation at the hypoxanthine guanine phosphoribosyl transferase (HGPRT) locus and unscheduled DNA synthesis (UDS)--were used. Treatment of rat and rabbit aorta smooth muscle cells with BaP (1-6 micrograms/ml) resulted in a significant increase of SCEs, HGPRT mutations and UDS. So smooth muscle cells are capable of converting BaP to metabolites with a DNA-damaging action. In order to investigate the relation between the formation of mutagenic BaP metabolites and the susceptibility to atherosclerosis we compared the mutagenic potential of BaP using aorta smooth muscle cells of different species (rat, rabbit) and locations (thoracic and abdominal aorta). Rabbits and abdominal aortas are more susceptible to atherosclerosis than rats and thoracic aortas. The SCE, HGPRT and UDS assays revealed that smooth muscle cells of different origin possessed the same metabolic potential towards BaP. There was no correlation between the mutagenic potency of BaP metabolites and the susceptibility to atherosclerosis. As smooth muscle cells have a low metabolic capacity towards BaP, probably other factors in addition to the metabolic capacity of smooth muscle cells are responsible for species and tissue differences in susceptibility to atherosclerosis.
Zwijsen
R M
RM
Department of Toxicology, Agricultural University, Wageningen, The Netherlands.
van Kleef
E M
EM
Alink
G M
GM
D000818:Animals; D001011:Aorta; D001161:Arteriosclerosis / Q000209:etiology / Q000378:metabolism; D001564:Benzo(a)pyrene / Q000493:pharmacokinetics* / Q000633:toxicity; D001711:Biotransformation; D004247:DNA / Q000096:biosynthesis; D005796:Genes / Q000187:drug effects; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D009152:Mutagenicity Tests; D009153:Mutagens; D009154:Mutation; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012854:Sister Chromatid Exchange
D009153:Mutagens; D001564:Benzo(a)pyrene; D004247:DNA; D007041:Hypoxanthine Phosphoribosyltransferase