The modification of the renal carcinogenicity of dimethylnitrosamine by actinomycin D and a protein deficient diet

Abstract

The effect of a single treatment with 30 mg dimethylnitrosamine (DMN) and 6 mug actinomycin D (ACT), given at different time intervals (ACT application to DMN, 2 h before, simultaneously, 5, 9 or 48 h later), was tested in female Sprague-Dawley rats in relation to renal carcinogenesis; additionally, the animals were fed either a normal or a protein deficient diet. The ACT treatment did not significantly modify either the kidney tumour incidence or the survival time in the different groups fed a normal diet. Nevertheless, there are indications that additional ACT application may shorten the latency period for DMN induced renal neoplasms or, when administered 5 h later than DMN, a slightly decreased and delayed tumour induction can be assumed. In groups fed a protein deficient diet, a significantly higher percentage of kidney tumour bearing animals as well as a shortened latency period were found when compared with the DMN group on normal diet, but these differences were independent of the additional ACT treatment 9 h later than DMN and were due to the protein deprivation. Morphologically, the tumours were of epithelial and mesenchymal type with a clear preponderance of the former type. Biochemical and morphological aspects are discussed.