Formation of DNA adducts and oxidative DNA damage in rats treated with 1,6-dinitropyrene.
In vitro metabolism studies have indicated that the tumorigenic environmental pollutant 1,6-dinitropyrene has the potential to bind covalently to DNA and to induce oxidative DNA damage. We have determined if 1,6-dinitropyrene treatment will cause both types of DNA damage in vivo. Female Sprague-Dawley rats were given a single intraperitoneal injection of 1,6-dinitropyrene, and covalent DNA adduct formation, as indicated by the presence of N-(deoxyguanosin-8-yl)-1-amino-6-nitropyrene, and oxidative DNA damage, as indicated by increases in 5-hydroxymethyl-2'-deoxyuridine and 8-hydroxy-2'-deoxyguanosine, were assessed at 3, 12, 24 and 48 h after dosing. 32P-postlabeling analyses of DNA isolated from liver, mammary gland, bladder and nucleated blood cells indicated the formation of N-(deoxy-guanosin-8-yl)-1-amino-6-nitropyrene, with the levels being highest in the bladder. 5-hydroxymethyl-2'-deoxyuridine was detected in DNA from each of these tissues, and the levels of this oxidized nucleoside were higher in the mammary glands and livers of 1,6-dinitropyrene-treated rats. 1,6-Dinitropyrene dosing did not affect the levels of 8-hydroxy-2'-deoxyguanosine in these two tissues. These results indicate that exposure to 1,6-dinitropyrene can result in increased levels of 5-hydroxymethyl-2'-deoxyuridine in addition to covalent DNA adduct formation.
Djurić
Z
Z
Department of Internal Medicine, Wayne State University, Detroit, MI 48201.
Potter
D W
DW
Culp
S J
SJ
Luongo
D A
DA
Beland
F A
FA
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D004247:DNA / Q000378:metabolism*; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis; D005260:Female; D008099:Liver / Q000187:drug effects; D010084:Oxidation-Reduction; D011721:Pyrenes / Q000032:analysis / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013936:Thymidine / Q000031:analogs & derivatives / Q000032:analysis; D001743:Urinary Bladder / Q000187:drug effects
D011721:Pyrenes; C018080:5-hydroxymethyl-2'-deoxyuridine; C033309:1,6-dinitropyrene; C045229:N-(deoxyguanosin-8-yl)-1-aminopyrene; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D003849:Deoxyguanosine; D013936:Thymidine