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.