Renal Transplacental Carcinogenicity of 3,3-Dimethyl-1-Phenyltriazene in Rats: Relationship of Renal Mesenchymal Tumor to Congenital Mesoblastic Nephroma and Intralobar Nephrogenic Rests

Abstract

Exposure of rat embryos to 3,3-dimethyl-1-phenyltriazene (DMPT) results in numerous malformations, but the urogenital system is not affected. In contrast, exposure of rat fetuses to DMPT has been reported to result in renal neoplasms, which were not further classified. To better understand this discrepancy in organotropism of the teratogenic and transplacental carcinogenic processes, the present study was undertaken to characterize the neoplasms induced in rat fetuses exposed to DMPT in utero. Renal neoplasms and persistent mesenchyme were observed in 19.2 and 11.5%, respectively, of the offspring of rats treated with 1 mg DMPT/ kg body weight intraperitoneally on gestation days 16, 18, and 20. The majority of these renal lesions were observed in females. The renal neoplasms were mixtures of various types of mesenchymal tissue derivatives including smooth muscle and fibrous connective tissue. These neoplasms would be classified as renal mesenchymal tumors in rats. Brain neoplasms (numerous types), compound odontomas, and micrognathism were observed predominantly in male offspring from the same group. This treatment also resulted in decreased body weights, increased incidence of sudden loss of body weight, tremors and ataxia, and hypoplastic testes. Exposure to single intraperitoneal doses of DMPT on gestation day 20 did not produce a classic dose-response pattern: Minimal effects were observed with 10 mg DMPT/kg (occasional renal mesenchymal tumors and brain neoplasms), marked effects were observed with 30 mg DMPT/kg (lower incidence rate of most of the alterations observed with 1 mg/kg on gestation days 16, 18, and 20), and no effects were observed with 60 mg DMPT/kg. DMPT administered intraperitoneally at 1 mg/kg body weight on gestation days 16, 18, and 20 is an animal model of transplacental chemically induced renal neoplasms, which provide lesions with similarities to both intralobar nephrogenic rests and congenital mesoblastic nephroma of humans. Why the kidney is a carcinogenic target and not a teratogenic target remains unknown.

Keywords

Wilms' tumor nephroblastoma methylating neurooncogenesis odontoma micrognathism testicular hypoplasia

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