TRANSPLACENTAL CARCINOGENESIS BY CISPLATIN IN F344 NCR RATS - PROMOTION OF KIDNEY TUMORS BY POSTNATAL ADMINISTRATION OF SODIUM BARBITAL/

Transplacental carcinogenic effects of cis-dichlorodiammineplatinum (c is-DDP) in F344 rats were investigated. Pregnant F344 rats were given a single ip administration of either cis-DDP (5 mg/kg body wt; group 1 ) or saline only (group 2) on Day 18 of gestation, Offspring of groups 1 and 2 were randomly and equally divided into two subgroups: 1a, 1b and 2a, 2b, respectively, Beginning at 4 weeks of age, offspring in gr oups 1b and 2b received 500 ppm of sodium barbital (NaBB) in diet, whi le those in groups 1a and 2a received normal diet. The experiment was terminated at 79 weeks of age. A low incidence (2/19; 10.5%) of male o ffspring exposed to transplacental cis-DDP (group 1a) developed renal cell adenomas, Postnatal administration of NaBB significantly enhanced this incidence (10/22; p < 0.01) in cis-DDP-initiated offspring. Also , multiple kidney tumors were more common in group 1b than any other g roup and three animals in this group developed frank renal cell carcin omas, cis-DDP, administered transplacentally, was a complete carcinoge n for rat liver as the incidence of hepatocellular adenomas was signif icantly higher in offspring exposed transplacentally to cis-DDP than i n those exposed to saline (20/82 vs 3/75; p < 0.05). NaBB, a known pro moter of hepatocellular carcinogenesis in adult rats initiated with N- nitrosodiethylamine, failed to promote liver carcinogenesis initiated by transplacental cis-DDP. Tumors of the central nervous system (3/82; gliomas) and peripheral nervous system (2/82; schwannomas) were found only in offspring exposed transplacentally to cis-DDP. Thus, cis-DDP, administered transplacentally, was a strong initiator of renal cell t umors and a complete carcinogen for multiple organs in rat offspring. (C) 1995 Academic Press, Inc.