Localization of cytochrome P450 1A1 in a specific region of hydronephrotic kidney of rat neonates lactationally exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin.
Hydronephrosis is typically observed in terata caused by in utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), via the arylhydrocarbon receptor, but the molecular mechanism underlying its pathogenesis is largely unknown. In the present study, pregnant Holtzman rats were treated once by gavage with TCDD (1.0 microg/kg bw) or corn oil on gestation day 15. All dams were allowed to litter, and standardized litters in terms of litter size were then reciprocally cross-fostered on postnatal day (PND) 1. On PND1, pups were divided into four experimental groups: pups exposed only in utero, pups exposed only lactationally, pups not exposed via either route (vehicle control), and pups exposed via both routes. Pups were euthanized on PND21 for further analyses. The TCDD dose used was not overtly toxic to the dams or neonates. The incidence and severity of hydronephrosis were markedly high in pups exposed to TCDD lactationally, but not those exposed in utero. On PND21, cytochrome P450 (CYP) 1A1 was detected predominantly in the outer zone of the medulla of the kidney from all the pups lactationally exposed to TCDD, regardless of the occurrence of hydronephrosis. Interestingly, TCDD concentrations in the cortex, the outer zone of the medulla and the inner zone of the medulla were similar. When adult Holtzman rats were administered TCDD, the induction of CYP1A1 was immunohistochemically detected in the liver but not in the kidney 7 days postadministration. The present findings suggest that TCDD-inducible genes via an AhR-dependent mechanism may be associated with the etiology of hydronephrosis in a particular region of the kidney.
Nishimura
Noriko
N
Endocrine Disruptors and Dioxin Research Project, National Institute for Environmental Studies, Tsukuba 305-8506, Japan.
Yonemoto
Junzo
J
Nishimura
Hisao
H
Tohyama
Chiharu
C
D000818:Animals; D000831:Animals, Newborn; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism*; D004785:Environmental Pollutants / Q000493:pharmacokinetics / Q000633:toxicity*; D005260:Female; D006869:Hydronephrosis / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D007774:Lactation; D008297:Male; D000072317:Polychlorinated Dibenzodioxins / Q000493:pharmacokinetics / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D021381:Protein Transport; D051381:Rats; D017207:Rats, Sprague-Dawley
D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; D019363:Cytochrome P-450 CYP1A1