Is N-methyl-N'-nitro-N-nitrosoguanidine a hormonal carcinogen? (Review).

The hormonal aspect of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) is discussed in relation to its carcinogenic potency for the gastric epithelium. The action of MNNG, as assessed in terms of a) the affinities for both the glucocorticoid receptor and androgen receptor of mouse, b) the effects on the turnover of hydrocortisone and dihydrotestosterone in the glandular stomach of mouse, c) the induction of ornithine decarboxylase in the same tissue, and d) the interfering effect on the hydrocortisone - linked acceleration of water turnover at the whole body level of a mouse, points to the steroid-mimetic nature of the carcinogen. It is suggested that MNNG may behave like an androgen antagonist on the one hand, and like a chimera between glucocorticoid agonist and glycocorticoid antagonist on the other hand. The proposition that a chemical carcinogen may have an interplay with the steroid and thyroid hormone receptor superfamily in the induction of malignant transformation is reviewed in the light of recent progress of steroid receptor biology.