Arteriosclerotic plaque development is 'promoted' by polynuclear aromatic hydrocarbons.
In previous work we found that weekly injections of the polynuclear aromatic hydrocarbon (PAH) carcinogen 7,12-dimethylbenz[a]anthracene (DMBA) induced spontaneous aortic plaques in cockerels to grow to a larger size and at a faster rate than plaques in control animals. To determine whether plaque-stimulating ability is related to carcinogenic potency or mutagenicity we have now tested a variety of agents, including PAH carcinogens, non-PAH carcinogens and weakly carcinogenic PAHs. Cockerels were injected weekly (from 4-20 weeks of age) with one of the following compounds: benzo[a]pyrene (B[a]P), benzo[e]pyrene (B[e]P), dibenz[a,h]anthracene (AH), dibenz[a,c]anthracene (AC), 3-methylcholanthrene (MCA), acetylaminofluorene (AAF), N-methyl-N,N'-nitro-nitrosoguanidine (MNNG) or anthracene (ANT). Plaques were present in the abdominal aortas of all animals. Plaque volumes were 8-14 times greater in AC-, B[a]P-, B[e]P-, MCA- and AH-treated cockerels than in controls. Plaques were slightly larger in the AAF-treated group than in control animals, and in the ANT- and MNNG-treated groups were indistinguishable in size from plaques in control animals. The largest plaque volumes were in AH-treated cockerels and were comparable in size to those elicited by DMBA treatment. The accelerated development of plaques is consistent with a 'promotional' role for these agents. There was a poor correlation between mutagenicity or carcinogenicity and plaque 'promotion', which may reflect a role for different metabolites in these processes.
D015073:2-Acetylaminofluorene / Q000633:toxicity; D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000818:Animals; D000873:Anthracenes / Q000633:toxicity; D001161:Arteriosclerosis / Q000139:chemically induced* / Q000473:pathology; D001551:Benz(a)Anthracenes / Q000633:toxicity; D001580:Benzopyrenes / Q000633:toxicity; D002273:Carcinogens / Q000633:toxicity*; D002645:Chickens; D008297:Male; D008748:Methylcholanthrene / Q000633:toxicity; D008769:Methylnitronitrosoguanidine / Q000633:toxicity; D011083:Polycyclic Compounds / Q000633:toxicity*
D000873:Anthracenes; D001551:Benz(a)Anthracenes; D001580:Benzopyrenes; D002273:Carcinogens; D011083:Polycyclic Compounds; D008769:Methylnitronitrosoguanidine; D008748:Methylcholanthrene; D015127:9,10-Dimethyl-1,2-benzanthracene; D015073:2-Acetylaminofluorene; C034020:anthracene