Fate of adriamycin-induced dilated renal pelvis in the fetal rat: functional and morphological effects in the offspring.
Previously we reported that gestational exposure to Adriamycin, an anthracycline antibiotic used in the treatment of neoplasms, reduced renal function in the neonatal rat, and we suggested that alterations in the development of the renal papilla might be responsible for the dysfunction. In this study we exposed groups of Sprague-Dawley rats to 0, 1.0, 1.25, or 1.5 mg/kg of Adriamycin on gestation days 10-12, a period previously shown to be effective in altering postnatal renal function with this compound. Offspring were evaluated at several developmental periods in order to 1) precisely define the morphological status of the urogenital system in Adriamycin-treated offspring; 2) replicate the finding of a decreased renal concentrating ability in the neonates; 3) determine the transience/permanence of any morphological effect; and 4) correlate any permanent alterations in urogenital morphology with our indicator of neonatal functional competence. Maternal Adriamycin treatment induced alterations in the development of the renal papilla that persisted well into the postnatal life of the offspring. The first appearance of the morphological alteration occurred in the absence of other general indicators of developmental toxicity such as growth retardation. The determination of the ultimate fate and functional consequences of the structural alterations required postnatal evaluations of the renal system. Finally, a relatively simple test of renal function in the neonate proved to be predictive of the permanence of the morphological effect, and the absolute test result showed a strong correlation with the incidence of the morphological effect in the overall population.
Kavlock
R J
RJ
Perinatal Toxicology Branch, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711.
Rehnberg
B F
BF
Rogers
E H
EH
D000014:Abnormalities, Drug-Induced / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D000831:Animals, Newborn; D004317:Doxorubicin / Q000633:toxicity*; D005260:Female; D007671:Kidney Concentrating Ability; D007682:Kidney Pelvis / Q000002:abnormalities* / Q000503:physiopathology; D008297:Male; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D013723:Teratogens
D013723:Teratogens; D004317:Doxorubicin