Retinyl acetate inhibits mammary carcinogenesis induced by N-methyl-N-nitrosourea

Abstract

THE use of pharmacological agents to prevent development of epithelial cancer is attracting increasing attention. Recent studies have shown the successful use of vitamin A and its synthetic analogues (together known as retinoids) for this purpose^1,2. We have shown that both natural and synthetic retinoids (retinyl acetate and retinyl methyl ether, respectively) markedly inhibit mammary carcinogenesis induced in the Sprague-Dawley rat by 7,12-dimethylbenz [a] anthracene (DMBA) (refs 3, 4). Although the DMBA model has contributed significantly to the understanding of mammary carcinogenesis, particularly hormone responsiveness, the model is less than ideal in that the tumours only rarely invade surrounding tissues and do not metastasise. A new mammary carcinogenesis model, first described by Gullino et al.⁵, using intravenous injection of N-methyl-N-nitrosourea (NMU) in the Buffalo rat, satisfies the deficiencies of the DMBA model in that cancers are exclusively localised in the mammary gland, are hormone dependent, show metastasis to other organs, are transplantable, and result in hypercalcaemia. NMU also causes a high incidence of mammary cancers in female Sprague–Dawley and Fischer-344 rats⁵, but the biological characteristics of the cancers in these strains have not been described in detail. But, our preliminary studies using Sprague–Dawley rats indicated that NMU-induced mammary cancers are highly aggresive and similar histologically to those induced in the Buffalo rat. The NMU model of mammary cancer thus resembles the human disease more closely than the DMBA model. We describe here a study of the effect of a retinyl acetate on mammary carcinogenesis induced by NMU, using a modification of the procedure reported by Gullino et al.⁵. We show that retinyl acetate inhibits carcinogenesis in this system.