DNA adduct formation and persistence in rat tissues following exposure to the mammary carcinogen dibenzo[a,l]pyrene

Citation
Jm. Arif et al., DNA adduct formation and persistence in rat tissues following exposure to the mammary carcinogen dibenzo[a,l]pyrene, CARCINOGENE, 20(6), 1999, pp. 1147-1150
Citations number
31
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
CARCINOGENESIS
ISSN journal
0143-3334 → ACNP
Volume
20
Issue
6
Year of publication
1999
Pages
1147 - 1150
Database
ISI
SICI code
0143-3334(199906)20:6<1147:DAFAPI>2.0.ZU;2-F
Abstract
Dibenzo[alpha,l]pyrene (DBP), an environmentally significant polycyclic aro matic hydrocarbon (PAH), is one of the most potent carcinogens with greater carcinogenicity in rodent mammary glands and skin than 7,12-dimethylbenz[a lpha]anthracene or benzo[alpha]pyrene, respectively. In this study, we have examined the formation and persistence of stable DNA adducts in rats admin istered a carcinogenic intramammiliary (i.m.) dose of DBP (0.25 mu mol/glan d). P-32-post-labeling analysis of mammary epithelial DNA 6 h, and 2, 5 and 14 days post-treatment produced one major (similar to 30%) and at least si x minor adducts, Non-target tissue DNA (lung, heart, bladder and pancreas) also showed essentially the same adduct pattern as did mammary DNA, except liver which resulted in four additional adduct spots. The mammary DNA was m ost adducted (2640 +/- 532 adducts/10(9) nucleotides) on day 5 while the ot her tissue DNAs had 10- to 65-fold lower adduct levels (lung > liver > hear t > bladder > pancreas). Adduct levels continued to increase at all time po ints examined for all tissues, except mammary tissue which showed a decline (similar to 40%) on day 14, Chromatographic comparison with adducts formed iii vitro by reaction of syn- and anti-DBP-11,12-diol-13,14-epoxides (DBPD Es) with DNA and individual nucleotides indicated that the ill vivo adducts were deoxyadenosine- and deoxyguanosine-derived, formed by interaction wit h both the anti- and syn-isomers; the adenine-derived adducts comprised 60- 75% of the total adducts, However, the Liver-specific DNA adducts (nos 8-11 ) were not derived from any of the DBPDE isomers, Our data show: (i) signif icantly higher DBP-DNA adduction in mammary tissue as compared with non-tar get tissues, which is consistent with its mammary carcinogenicity; (ii) ade nine is highly reactive towards DBP metabolites as has been observed for ma ny other PAHs; and (iii) the peak binding of DBP with DNA was shifted beyon d 14 days for the nontarget tissues by i.m, route of exposure.