Abstract
Seven days on a protein-free diet increases the susceptibility of rats to the action of DMN as a renal carcinogen. The dose response for the induction of kidney tumours by a single dose of dimethylnitrosamine (DMN) in these rats is reported. The first tumour was not found until 28 weeks after the dose. At 100 weeks the incidence ranged from 22.5% at the lowest dose (20 mg/kg) to 97% at the highest dose (60 mg/kg). The incidence in probits at any time between 50 and 100 weeks was linearly related to the log dose. Epithelial and mesenchymal tumours were produced in an approximate ratio of 2:1. The protein-free diet alters the rate of metabolism of DMN in the rat, and increases the alkylation of nucleic acids by this carcinogen in the kidney. Further treatment of the rat with benzo(a)pyrene can reverse, to some extent, the change in metabolism, but does not reverse the change in alkylation. It is shown that the change in kidney-tumour incidence produced by the change in diet, and by the treatment with benzo(a)pyrene, corresponds to the changes these treatments produce in the alkylation of kidney DNA by the carcinogen.
Highlights
Summary.-Seven days on a protein-free diet increases the susceptibility of rats to the action of DMN as a renal carcinogen
Produced only a 20%0 incidence of kidney tumours. This low incidence of tumours, and the many severe changes in the metabolism of the animal produced by the near lethal dose, limited the usefulness of this means of inducing cancer
The diet influences the effectiveness of the nitrosamine as a renal carcinogen in 2 ways: it allows the rat to tolerate a much larger dose (McLean & Verschuuren, 1969); and it alters the pharmacokinetics of the nitrosamine so that the proportion of any dose activated to the proximal carcinogen in the kidney is greatly increased
Summary
Animals.- Wistar-derived male rats of CFN stock (5-6 wNeeks old; 130-140 g) were bought from Carworth Farms, New City, N.Y., U.S.A. After 5-7 days' acclimatization, during which they were fed Purina Chow (Ralston Purina Corp., St Louis, Mo., U.S.A.), they were changed to a semi-synthetic diet containing no protein (McLean & McLean, 1966) Those rats to be treated were weighed and given an i.p. injection of a solution of DMN in 015M NaCl (0.5 ml/100 g body wt) on the morning of the 7th day on the diet. (Controls were injected with a similar volume of 0-15M NaCl at the same time.) After a further 5 days on this diet (i.e. a total of 12 days) the rats were returned to the normal diet of Purina Chow. While they were receiving the protein-deficient diet the rats were kept in cages with gridded bottoms so that they were unable to eat faeces or bedding
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call