Possible application to medium-term organ bioassays for renal carcinogenesis modifiers in rats treated with N-ethyl-N-hydroxyethylnitrosamine and unilateral nephrectomy

Abstract

The effects of the renal tumor promoters; beta-cyclodextrin (beta-C), DL-serine (DL-S), basic lead acetate (LA), trisodium nitrilotriacetate monohydrate (NTA) and potassium bromate (KB), and diethylene glycol (DEG) as a negative control, on early stage of renal carcinogenesis were investigated in unilaterally nephrectomized male Wistar rats after N-ethyl-N-hydroxyethylnitrosamine (EHEN) administration. Wistar male rats were fed 1000 ppm EHEN diet for 2 weeks and the left kidney was removed at week 3, then the animals were divided into 7 groups of 15 rats each. These groups received the following treatments: 1000 ppm LA, 10000 ppm NTA or 500 ppm KB diet for 18 weeks from week 3; 45 mg/100 g body wt./day of beta-C injected sc for 7 days; 100 mg/100 g body wt. of DL-S injected sc biweekly for 6 weeks; 5% DEG in drinking water as a negative control for two days. Five rats in each group were killed at weeks 8, 12 and 20 and their kidneys were examined histologically. At week 20, the average numbers of adenomatous hyperplasias seen as preneoplastic lesions in the beta-C, DL-S, LA, NTA or KB groups were significantly higher than those in the DEG or control groups. Thus within a relatively short period of 20 weeks, promoting effects of chemicals can be detected as a significant increase of adenomatous hyperplasias in this model.