Enhancement of hepatic and renal tumorigenesis with thyroidectomized NZR/Gd rats treated with dimethylnitrosamine.

Endocrine modulation of DMN carcinogenesis was studied in NZR/Gd rats preconditioned by starving 48 hr and then injected i.p. once with 20 mg DMN/kg. Intact rats developed kidney tumors (44% TBA), most of tubular epithelial type resembling human tumors rather than mesenchymal. Thyroidectomy (Tx) 45 days before DMN significantly enhanced DMN carcinogenesis, renal carcinoma incidence increasing to 69%. Renal carcinomas showed more signs of malignancy in Tx rats. Other neoplastic responses useful for further studies including tumors in nasal epithelium (13%), liver (18%, increased to 59% in Tx rats), and lung (40%): these tumors were rare or not previously reported in single-dose experiments in other rat strains. A sex difference in lung tumor incidence (male 70%, female 16%) was statistically significant and thyroidectomy reduced the sex-differential (to 54% and 39% respectively). The increased incidence of kidney and liver tumors could be due to altered metabolism of DMN in tissues of Tx rats.