GENOTOXICITY INDUCED IN HUMAN LYMPHOBLASTS BY ATMOSPHERIC REACTION-PRODUCTS OF NAPHTHALENE AND PHENANTHRENE

The genotoxic risks from exposure to polycyclic aromatic hydrocarbons (PAH) have long been recognized. Less well understood are the potentia l genotoxic risks of the atmospheric reaction products of this class o f compounds. In this investigation, we have utilized several human cel l genotoxicity assays to evaluate naphthalene, phenanthrene, and their atmospheric reaction products 1-nitronaphthalene, 2-nitronaphthalene, 1-hydroxy-2-nitronaphthalene, 2-hydroxy-1-nitronaphthalene, 1,4-napht hoquinone and 2-nitrodibenzopyranone. In addition, reaction products o f naphthalene were generated in a 6700-1 Teflon environmental chamber, collected on a solid adsorbent, extracted and fractionated by normal- phase HPLC. Individual fractions were then analyzed using GC-MS, and t ested for genotoxicity. Genotoxicity was determined using the human B- lymphoblastoid cell line, MCL-5, which expresses several transfected P 450 and epoxide hydrolase genes. Mutagenicity was evaluated at both th e heterozygous tk locus and the hemizygous hprt locus, permitting dete ction of both intragenic and chromosomal scale mutational events. Test compounds were also screened using the CREST modified micronucleus as say. Genotoxicity results indicate that 2-nitronaphthalene and 2-nitro dibenzopyranone possess greater mutagenic potency than their parent co mpounds, and interestingly, both compounds induced significant increas es in mutation frequency at tk but not hprt. These results suggest a m echanistic difference in human cell response as compared to bacteria, where both compounds were previously shown to induce point mutations i n the Salmonella reversion assay. The genotoxicity of 2-nitronaphthale ne and 2-nitrodibenzopyranone in human cells, together with their high concentrations in ambient air relative to nitro-PAH directly emitted from combustion sources, emphasizes the need to consider atmospheric r eaction products of PAH in genotoxicity assessments. (C) 1997 Elsevier Science B.V.