Oxidative DNA damage in male Wistar rats exposed to di-n-butyl phthalate.
Dialkyl phthalate esters are used in the plastic industry and widely distributed in the environment. Previously, it has been shown that di-n-butyl phthalate (DBP) produces testicular atrophy and liver enlargement in rodents, and the mechanisms behind this could involve reactive oxygen species (ROS). In this study, oxidative DNA damage was measured in terms of the premutagenic modified nucleoside 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxodG) in nuclear DNA from liver, kidneys, and testes from rats exposed to DBP in the perinatal or preadult period. In one experiment, pregnant rats were administered 0 or 0.5 g DBP/kg/d by gavage from d 7 after conception to d 17 after delivery and organs from male offspring were analyzed. In a second experiment, 25-d-old rats were administered 0, 0.5, or 2 g DBP/kg/d by gavage for 10 d. After perinatal exposure, body and organ weights were unchanged. The 8-oxodG/10(6) dG ratio in liver DNA increased significantly in the exposed group. In contrast, the 8-oxodG/10(6) dG ratio was significantly decreased in kidney DNA, whereas it remained unchanged in the testis. After preadult exposure (postnatal d 25 to 34) the testes weight of the exposed animals were significantly decreased and severe atrophy of the seminiferous tubules was observed. The body weight of the animals in the high-dose group was significantly decreased compared to the control. The 8-oxodG levels in liver, kidney, and testis DNA remained unchanged. Although ROS has been suspected of being involved in the formation of testicular atrophy in phthalate-exposed rats, no apparent sign of oxidative DNA damage was found after phthalate exposure perinatally or during the preadult stage. With respect to phthalate-induced oxidative DNA damage in the liver, it appears that the developmental stage during exposure is important.
Wellejus
A
A
Institute of Public Health, University of Copenhagen, Copenhagen, Denmark.
Dalgaard
M
M
Loft
S
S
D000818:Animals; D002274:Carcinogens, Environmental / Q000008:administration & dosage / Q000633:toxicity*; D004249:DNA Damage / Q000187:drug effects*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism*; D003993:Dibutyl Phthalate / Q000008:administration & dosage / Q000633:toxicity*; D004781:Environmental Exposure / Q000009:adverse effects*; D005260:Female; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013737:Testis / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
D002274:Carcinogens, Environmental; D017382:Reactive Oxygen Species; D003993:Dibutyl Phthalate; D003849:Deoxyguanosine