MUTAGENICITY OF CYCLOPENTA-FUSED ISOMERS OF BENZ(A)ANTHRACENE IN BACTERIAL AND RODENT CELLS AND IDENTIFICATION OF THE MAJOR RAT-LIVER MICROSOMAL METABOLITES

  • 1 January 1984
    • journal article
    • research article
    • Vol. 44  (11) , 4993-5003
Abstract
The microsomal metabolites and mutagenic activity of 4 cyclopenta-fused benz(a)anthracenes, benz(j)aceanthrylene [B(j)A], benz(e)aceanthrylene [B(e)A], benz(l)aceanthrylene [B(I)A] and benz(k)acephenanthrylene [B(k)A], were studied. Aroclor 1254-induced rat liver microsomes metabolized B(j)A to B(j)A-1,2-dihydrodiol, B(j)A-9,10-dihydrodiol, B(j)A-11,12-dihydrodiol and 10-hydroxy-B(j)A; B(e)A to B(e)A-1,2-dihydrodiol, B(e)A-3,4-dihydrodiol and B(e)A-5,6-dihydrodiol; B(I)A to B(I)A-1,2-dihydrodiol, B(I)A-4,5-dihydrodiol and B(I)A-7,8-dihydrodiol; and B(k)A to B(k)A-4,5-dihydrodiol and B(k)A-8,9-dihydrodiol. With each polycyclic aromatic hydrocarbon, metabolism occurred on the cyclopenta ring. All 4 isomers were active as gene mutagens in Salmonella typhimurium and in Chinese hamster V79 cells. In the S. typhimurium mutation studies, using Aroclor 1254-induced rat liver S9, B(j)A, B(e)A and B(I)A required significantly less microsomal protein for maximal mutation response than B(k)A and B(a)P, suggesting a 1-step activation mechanism, presumably on the cyclopenta-fused ring. B(j)A, B(e)A and B(I)A were significantly more mutagenic than B(k)A and B(a)P in S. typhimurium. In the Aroclor 1254-induced rat liver S9-mediated V79 mutagenesis system, all 4 isomers were active, with B(I)A the most active. When Syrian hamster embryo cells were used as the metabolic activation component for V79 cells, only B(I)A produced a significant response and was equivalent in activity to B(a)P. A helical configuration for B(I)A is inferred from the identification of 2 trans-B(I)A-1,2-dihydrodiols, syn and anti, which were synthesized, separated and characterized. The metabolically formed dihydrodiol is anti-trans-B(I)A-1,2-dihydrodiol and experimental evidence suggests that the metabolically formed B(I)A-1,2-oxide is the anti-ismer. Synthetic B(I)A-1,2-oxide was found to be a direct-acting mutagen in S. typhimurium and Chinese hamster V79 cells and is estimated to account for up to 40% of the mutagenic activity of the parent hydrocarbon. Therefore, certain cyclopenta-ring fusions on benz(a)anthracene appear to markedly increase its genotoxic and carcinogenic activities. [The role of these compounds as environmental pollutants was described.].