title: Characterization of a major aromatic DNA adduct detected in human breast tissues.
abstract: A bulky DNA adduct (Spot 1) was previously detected in normal adjacent breast tissues of 41% (36/87) of women with breast cancer and in none (0/29) of the noncancer controls by (32)P-postlabeling. To characterize this adduct, it was chromatographically compared with DNA adduct profiles generated in several in vitro and in vivo experimental systems. First, MCF-7 cells were exposed to a number of chemical carcinogens, that is, benzo[a]pyrene (B[a]P), 4-OH-B[a]P, 9-OH-B[a]P, 11-OH-B[a]P, B[a]P-trans-4,5-dihydrodiol, 1-nitropyrene, 6-nitrochrysene, dibenzo[a,l]pyrene, benzo[c]phenanthrene, dibenzo[a,h]anthracene, 3-methylcholanthrene, and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine. Spot 1 was detected as a minor adduct in cells treated with B[a]P but not other compounds. Second, to determine whether Spot 1 is derived from lipid peroxidation products or estrogen metabolites, it was compared with adduct profiles of cells or DNAs exposed to 17beta-estradiol, 4-hydroxy estradiol, 4-hydroxynonenal, or oxidized oat oil. Spot 1 was not detectable in these samples. In addition, Spot 1 did not comigrate with the 1,N(2)-ethenodeoxyguanosine adduct standard. Third, to explore the mechanism of Spot 1 formation, it was compared with adduct profiles detected in DNA or mononucleotides reacted with BPDE, 1-OH-7,8-dihydrodiol of B[a]P, and 3-OH-7,8-dihydrodiol of B[a]P as well as in rats orally treated with B[a]P. Spot 1 comigrated with a minor adduct in BPDE-treated DNA during anion exchange rechromatography but these two adducts were separated by partition chromatography. Spot 1 also behaved in a manner that was very similar to that of the polar B[a]P adducts detected in rat liver, but the two adducts were separated by HPLC. Fourth, Spot 1 was compared with CD1 mice exposed to 7H-benzo[c]fluorene (B[c]F). Spot 1 from some patients comigrated with a major adduct induced by B[c]F. Finally, we found that the presence of Spot 1 in human breast tissues was not related to smoking status but, rather, with CYP1A1 MspI polymorphism. The CYP1A1 mutant carriers had a significantly higher frequency of this adduct than did the wild-type genotypes. Furthermore, individuals with Spot 1 had a significantly higher staining intensity for BPDE-PAH adducts in their tissue sections than those without it. These results demonstrate that this major bulky DNA adduct detected in human breast tissues is related to PAH exposure.
authors.affiliation: Department of Gastrointestinal Medical Oncology, University of Texas, M.D. Anderson Cancer Center, Houston, Texas 77030, USA. dli@mdanderson.org
authors.forename: Donghui
authors.initials: D
authors.lastname: Li
authors.forename: Mianying
authors.initials: M
authors.lastname: Wang
authors.forename: Pervez Firoz
authors.initials: PF
authors.lastname: Firozi
authors.forename: Ping
authors.initials: P
authors.lastname: Chang
authors.forename: Weiqing
authors.initials: W
authors.lastname: Zhang
authors.forename: Wanda
authors.initials: W
authors.lastname: Baer-Dubowska
authors.forename: Bhagavatula
authors.initials: B
authors.lastname: Moorthy
authors.forename: Suryanarayana V
authors.initials: SV
authors.lastname: Vulimiri
authors.forename: Regine
authors.initials: R
authors.lastname: Goth-Goldstein
authors.forename: Eric H
authors.initials: EH
authors.lastname: Weyand
authors.forename: John
authors.initials: J
authors.lastname: DiGiovanni
mesh_terms: D000818:Animals; D001564:Benzo(a)pyrene / Q000032:analysis; D001940:Breast / Q000737:chemistry* / Q000201:enzymology; D002274:Carcinogens, Environmental / Q000494:pharmacology; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D018736:DNA Adducts / Q000032:analysis*; D004260:DNA Repair; D004847:Epithelial Cells / Q000737:chemistry; D005260:Female; D006801:Humans; D051379:Mice; D008895:Milk, Human / Q000166:cytology; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology; D011084:Polycyclic Aromatic Hydrocarbons / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
chemical_list: D002274:Carcinogens, Environmental; D018736:DNA Adducts; D011084:Polycyclic Aromatic Hydrocarbons; C056612:benzo(a)pyrene-DNA adduct; C095911:polycyclic aromatic hydrocarbons-DNA adduct; D001564:Benzo(a)pyrene; D019363:Cytochrome P-450 CYP1A1