Characterization of naphtho[1,2-a]pyrene and naphtho[1,2-e]pyrene DNA adducts in C3H10T1/2 fibroblasts.
Polycyclic aromatic hydrocarbons (PAHs) are a class of carcinogenic chemicals that are ubiquitous in the environment. Fjord-region naphthopyrene isomers are structurally similar to the potent fjord-region PAH carcinogen dibenzo[a,l]pyrene and thus have the potential to be potent carcinogens. Naphtho[1,2-a]pyrene (N[1,2-a]P) exhibited similar bacterial mutagenicity and morphological cell transforming activity when compared to benzo[a]pyrene (B[a]P), whereas the structural isomer, naphtho[1,2-e]pyrene (N[1,2-e]P) was inactive is these bioassays. In this study, we examined the formation of DNA adducts in C3H10T1/2Cl8 (C3H10T1/2) mouse embryo fibroblasts exposed to N[1,2-a]P or N[1,2-e]P and their respective dihydrodiols. The DNA adducts were characterized by co-chromatography with reaction products from anti-N[1,2-a]P diol epoxide (DE) or anti-N[1,2-e]PDE and polydeoxyadenosine (dAdo) or oligodeoxyguanosine (dGuo). C3H10T1/2 fibroblasts exposed to N[1,2-a]P or N[1,2-a]P-9,10-diol produced both anti-N[1,2-a]P-DE-dAdo and -dGuo adducts with total DNA adduction levels of 22.2 to 33.3 pmol DNA adducts/mug DNA. C3H10T1/2 fibroblasts exposed to N[1,2-e]P produced 2 major and 1 minor adducts. C3H10T1/2 fibroblasts exposed to N[1,2-e]P-11,12-diol produced 2 major adducts. All of the identified adducts were anti-N[1,2-e]PDE-dGuo and -dAdo adducts. While the total DNA adduct level in N[1,2-e]P-11,12-diol-treated fibroblasts was extremely high, 105.9 pmol DNA adducts/mug DNA, the level in N[1,2-e]P-treated fibroblasts was 1.47 pmol DNA adducts/microg DNA. We conclude that lack of biological activity of N[1,2-e]P may be related to its inability to form sufficient amounts of N[1,2-e]P-11,12-diol, which would then be metabolized to sufficient amounts of anti-N[1,2-e]PDE needed to transform these fibroblasts.
Nelson
Garret
G
Environmental Carcinogenesis Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, MD-B143-06, Research Triangle Park, NC 27711, USA.
Ross
Jeffrey A
JA
Pimentel
Maria
M
Desai
Dhimant
D
Sharma
Arun K
AK
Amin
Shantu
S
Nesnow
Stephen
S
D000818:Animals; D002460:Cell Line; D018736:DNA Adducts / Q000737:chemistry*; D005347:Fibroblasts / Q000737:chemistry; D051379:Mice; D008809:Mice, Inbred C3H; D009281:Naphthalenes / Q000737:chemistry*; D011721:Pyrenes / Q000737:chemistry*
D018736:DNA Adducts; D009281:Naphthalenes; D011721:Pyrenes; C519128:naphtho(1,2-a)pyrene; C519129:naphtho(1,2-e)pyrene