INHIBITION OF N-METHYL-N'-NITRO-N-NITROSOGUANIDINE-ACTIVATED GUANYLATE-CYCLASE BY ANTI-CARCINOGENIC AGENTS

  • 1 January 1980
    • journal article
    • research article
    • Vol. 71  (3) , 356-361
Abstract
Nitroso chemical carcinogens markedly activate guanylate cyclase, which catalyzes the production of cyclic GMP. The effect of inhibitors of carcinogenic compounds on guanylate cyclase activation by N-methyl-N''-nitro-N-nitrosoguanidine (MNNG) were studied [in mouse liver homogenates]. An antioxidant group of anticarcinogenic compounds was effective. Disulfiram and phenethyl isothiocyanate exhibited the most potent inhibition. Inhibitor constants (Ki) for disulfiram and phenethyl isothiocyanate were 1.2 .times. 10-5 M and 4.9 .times. 10-5 M, respectively. Sodium diethyldithiocarbamate, phenyl isothiocyanate, butylated hydroxyanisole and ethoxyquin showed moderate inhibitory effects. Sodium selenide decreased the MNNG-activated guanylate cyclase activity to .apprx. 30%, and it was inhibitory at the low concentration of 10-5 M. One of the mechanisms by which anticarbinogenic compounds exert their effect may in part be related to the inhibition of guanylate cyclase.