Mutagenicity of C24H14 PAH in human cells expressing CYP1A1

Relatively little is known about the mutagenicity of C24H14 PAH, a diverse group of five- and six-ring PAH, some of which are present at trace levels in the environment. To better understand the mutagenicity of this class of compounds, 11 C24H14 PAH, including benzoa]perylene, benzob]perylene, dibenzoa,e]fluoranthene, dibenzoa,f]fluoranthene, dibenzoj,l]fluoranthene, dibenzoa,h]pyrene, dibenzoa,i]pyrene, dibenzoe,l]pyrene, naphtho1,2-b]fluoranthene, naphtho2,3-a]pyrene, and naphtho2,3-e]pyrene, were tested in a mutagenicity assay based on human h1A1v2 cells. h1A1v2 cells are a line of human B-lymphoblastoid cells that have been engineered to express cytochrome P4501A1 (CYP1A1), an enzyme capable of metabolizing promutagenic PAH. Mutagenicity was measured at the thymidine kinase (tk) locus following a 72-h exposure period. Our results show that nine of the compounds were mutagenic. Benzoa]perylene, dibenzoa,e]fluoranthene, dibenzoa,i]pyrene, and naphtho2,3-a]pyrene were the most potent mutagens, having minimum mutagenic concentrations (MMC) (i.e., the dose at which the induced response was twice that of the negative controls) in the 1-5 ng/ml range. Benzob]perylene, dibenzoa,h]pyrene, dibenzoa,f]fluoranthene, and naphtho2,3-e]pyrene were somewhat less potent mutagens, having MMC in the 10-30 ng/ml range. Dibenzoe,l]pyrene, which had an MMC of 280 ng/ml, was the least potent mutagen. Dibenzoj,l]fluoranthene and naphtho1,2-b]fluoranthene were not mutagenic at the doses tested (1-3000 ng/ml). The most mutagenic compounds were also quite toxic. At the highest doses tested, benzoa]perylene, dibenzoa,e]fluoranthene, dibenzoa,i]pyrene, dibenzoa,h]pyrene, and dibenzoa,f]fluoranthene induced > 60% killing, and naphtho2,3-a]pyrene and naphtho2,3-e]pyrene induced > 50% killing. Benzob]perylene, dibenzoe,l]pyrene, dibenzoj,l]fluoranthene, and naphtho1,2-b]fluoranthene induced < 50% killing at the highest doses tested. Comparing these results to a previous study in which nine other C24H14 PAH were tested for mutagenicity in this same assay, it was found that dibenzoa]pyrene isomers were generally more mutagenic than the other groups of C24H14 PAH tested. These observations are discussed with emphasis given to identifying C24H14 PAH that may be important environmental mutagens.