Inhibition of Growth of Rat by Oral Administration of Methyl-cholanthrene. Effects of Dietary Cystine and Methionine Supplements. ∗

Abstract

In the present communication it is desired to report preliminary results obtained in studies of the effects of certain carcinogenic substances on sulfur metabolism. The experimental approach employed in the first series of investigations is similar to that which has resulted in the demonstration that bromobenzene, 1 cholic acid, 2 naphthalene, 3 and iodoacetic acid 4 exert an inhibiting effect on the growth of the young white rat when any one of these compounds is incorporated into a basal diet of relatively low protein content. The addition of either 1-cystine or dl-methionine to the basal diet containing either bromobenzene, cholic acid, naphthalene, or iodoacetic acid resulted in a prompt stimulation of growth, despite the continued presence of the foreign organic compound in the diet. It was suggested that these organic substances are capable of producing a specific deficiency in the sulfur-containing amino acids, probably through the requirements of the organism for organic sulfur, in the form of cystine or methionine, for detoxication mechanisms. This conclusion is supported by the observation that inorganic sulfate, amino acid nitrogen in the form of a casein digest, and organic sulfur in the form of that found in taurine will not stimulate the growth of animals stunted by the administration of either bromobenzene, cholic acid or iodoacetic acid.

In the present studies, male rats at weaning have been placed on a basal diet of the following composition: casein† 6, starch 50, lard 24, sucrose 15, cod liver oil 1, and inorganic salts† 4%. In addition, each animal received a daily supplement of 400 mg of yeast.§ When the rats reached a body weight of 75 to 85g, methyl-cholanthrene was incorporated into the basal diet.