FORMATION OF DNA-ADDUCTS AND OXIDATIVE DNA-DAMAGE IN RATS TREATED WITH 1,6-DINITROPYRENE

In vitro metabolism studies have indicated that the tumorigenic enviro nmental pollutant 1,6-dinitropyrene has the potential to bind covalent ly 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 inject ion of 1,6-dinitropyrene, and covalent DNA adduct formation, as indica ted by the presence of N-(deoxyguanosin-8-yl)-1-amino-6-nitropyrene, a nd oxidative DNA damage, as indicated by increases in 5-hydroxymethyl- 2'-deoxyuridine and 8-hydroxy-2'-deoxyguanosine, were assessed at 3, 1 2, 24 and 48 h after dosing. P-32-postlabeling analyses of DNA isolate d from liver, mammary gland, bladder and nucleated blood cells indicat ed the formation of N-(deoxyguanosin-8-yl)-1-amino-6-nitropyrene, with the levels being highest in the bladder. 5-hydroxymethyl-2'-deoxyurid ine 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 af fect the levels of 8-hydroxy-2'-deoxyguanosine in these two tissues. T hese results indicate that exposure to 1,6-dinitropyrene can result in increased levels of 5-hydroxymethyl-2'-deoxyuridine in addition to co valent DNA adduct formation.