Chromosome aberrations induced in rat lymphocytes by N-nitroso compounds as a possible basis for carcinogen screening

Abstract

MANY N-nitroso compounds are toxic, carcinogenic, mutagenic and teratogenic, and several are known to give rise to alkylating intermediates in the body¹. The nitrosamines (for example, dimethylnitrosamine) require activation by enzymes before yielding these intermediates but nitrosamides (for example, N-methylnitrosourea) may react with nucleic acids and proteins without metabolic activation. The nature of the various intermediates between the nitroso compound and the intracellular methylating agent has not been established, however, and the question of the duration of their existence in the body arises. With dimethylnitrosamine, the acute lesion is mainly severe necrosis of the centrilobular zones of the liver, including damage to the hepatic sinusoids and central veins as well as to the centrilobular parenchymal cells^2,3. It therefore follows that at least one of the intermediates must be of sufficient stability to damage the vascular cells. Since dimethylnitrosamine is active in the host-mediated assay for mutagenesis⁴ an active intermediate must also be capable of passing into the peritoneal cavity. N-methylnitrosourea is mutagenic in bacteria⁵ and is known to induce chromosomal aberrations in mammalian and plant cells in vitro^6,7.