Promotion by sodium barbital induces early development but does not increase the multiplicity of hereditary renal tumors in Eker rats

Citation
Dc. Wolf et al., Promotion by sodium barbital induces early development but does not increase the multiplicity of hereditary renal tumors in Eker rats, CARCINOGENE, 21(8), 2000, pp. 1553-1558
Citations number
40
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
CARCINOGENESIS
ISSN journal
01433334 → ACNP
Volume
21
Issue
8
Year of publication
2000
Pages
1553 - 1558
Database
ISI
SICI code
0143-3334(200008)21:8<1553:PBSBIE>2.0.ZU;2-V
Abstract
Induced cell proliferation is important in the mode of action of many non-g enotoxic renal carcinogens. Since Tsc2 mutant (Eker) rats are genetically p redisposed to the development of renal cell tumors, they provide a useful a nimal model in which to study the action of renal carcinogens. Sodium barbi tal was used as a model non-genotoxic renal carcinogen to test whether a co ncentration that increased renal tubular proliferation without severe nephr otoxicity would enhance tumor induction in a hereditary tumor model. First, a subchronic concentration-response study was conducted in wild-type male Long-Evans rats to determine increased cell proliferation without severe ne phrotoxicity, Rats were dosed with sodium barbital in the feed at 0, 50, 25 0, 500, 1000, 2000 or 4000 p.p.m. for 3 or 8 weeks. Cell proliferation with in the cortex and nephrotoxicity were quantitated, Enhanced proliferation w ith minimal nephrotoxicity occurred at 500 p.p.m., A second study was condu cted in male Tsc2 mutant rats given sodium barbital in the feed at 0, 100 o r 500 p.p.m. from 9 weeks of age to either 6 or 12 months of age. An additi onal group of rats was treated with sodium barbital for 6 months and then p rovided control feed until 12 months of age, Rats necropsied at 6 months of age had a concentration-dependent increase in preneoplastic and total rena l lesions. Sodium barbital-treated rats necropsied at 12 months of age had numbers of lesions that were not different from controls. Total combined pr eneoplastic and neoplastic lesions in the 6 month, high dose group was the same as the 12 month control group, These data show that sodium barbital ca used progression to the stage of spontaneous renal lesions in Tsc2 mutant r ats but did not increase their overall number. These data suggest that enha nced cell proliferation without significant cytotoxicity exerted a promotio nal influence in this hereditary model.