Hepatic pathology in rats on low dietary levels of dimethylnitrosamine.

Abstract

DIMETHYLNITROSAMINE (DMN) is a very powerful liver carcinogen for the rat (Magee and Barnes, 1956) and will produce malignant tumours at other sites and in other species (Magee and Barnes, 1967).Because of the possible importance of certain nitrosamines as aetiological agents for cancer in the human environment (Magee and Barnes, 1967) it was important that an attempt should be made to try to obtain experimental data on the basis of which it might be possible to calculate a non-effective dose of this compound. This also required an evaluation of non-neoplastic lesions appearing in animals exposed to the carcinogenic nitrosamine and their relation to tumour development. The experiments reported here were carried out in this laboratory since 1957 and dietary concentrations of DMN ranging between 2 and 50 p.p.m. were used. No non-neoplastic lesions were found to be specifically linked with the appearance of tumours. The findings are discussed in relation to the problem of constructing the dose-response relationship of a powerful carcinogen which in this case is probably produced within the animal body from the compound which is added to the diet. MATERIALS AND METHODSMale and female white rats (Porton strain) 4-6 weeks old were housed 6 to a cage. All rats were given Diet 41B (Bruce and Parkes, 1957) in powder form. Food intake was measured throughout the experiments and the rats were weighed twice weekly. All sick animals and any animal found to be losing weight were killed with coal-gas. DMN (British Drug Houses, Ltd.) was added to the powdered diet as a solution in arachis oil. The solutions in oil were so made up that oil was added at the rate of 10 ml. to each kilo of powdered diet and mixed in a Hobart food mixer. The controls had oil alone added to their diet except for one group of 6 male and 6 female included from another experiment which were fed pellets. At intervals during the earlier experiments the level of DMN in the diets was checked by the method of Heath and Jarvis (1955). The amount of DMN was always within 20% of the expected concentration and it did not fall off within the periods (1-2 weeks) during which the batches of prepared diets were used. PathologyAutopsies were carried out shortly after death and the tissues fixed in either Helly's solution or formol saline. Several pieces of the liver were removed and in * Present address: Section of Environmental Carcinogenesis, Istituto Nazionale Tumori,

Volatile Nitrogenous Bases and Aliphatic Secondary Amines of Burley Tobacco

“…Hi:LiJilffi+}:qT'$:?i::n'".[rk}ii{{"i;1,+"+{*H;'r#+};*1+:"'J"':'J'ffi';';""""? "?ii;"'""'i"'j3ffi'j';'-r"l:$l"r{ (6,18). However, from data on the acute effects of nitrosamines in short term experiments, the data obtained in this investigation indicate that there are sufficient aliphatic secondary amines present for the formation of biologically important quantities of alkyl nitrosamines either in smoke or in vivo (8,18).…”

Chronic Inhalation Toxicity of Unsymmetrical Dimethylhydrazine: Oncogenic Effects

“…The lowest dose given to rats was 2 ppm in their diet (Terracini et al, 1967). Concentrations used in this study ranged from 2 to 50 ppm.…”

Overview: N-Nitroso Compounds as Carcinogens for Experimental Animals and Man

“…In case of dimethylnitrosamine, Terracini et al [22] reported that 2 ppm in the diet caused liver tumor in 1 out of 37 rats, and 5 ppm in 5 out of 68 rats after an observation time of up to 120 weeks. Ito [personal commun.]…”