Activity and hormone responsiveness of adenyl cyclase during induction of tumors in rat liver with 3'-methyl-4-dimethylaminoazobenzene.

Abstract

Mature rats were fed a diet containing 0.06% (w/w) of the carcinogen 3′-methyl-4-dimethylaminoazobenzene for a period of 12 weeks. Between 13 and 26 weeks, 6 of the 11 rats not sacrificed earlier had developed malignant tumors. The basal activity and responsiveness to isoproterenol, glucagon, and fluoride of the adenyl cyclase in the 1100 × g fraction of liver homogenates from these animals were compared to those of control animals throughout the period. By 2 weeks after commencement of the diet, there was a 170% increase in the isoproterenol responsiveness of the cyclase which reached a maximum of 480% by 9 weeks. The activation of the enzyme by isoproterenol was blocked by propranolol. The basal activity of adenyl cyclase also rose during the diet, to reach a maximum of 270% of the controls at 9 weeks. The glucagon responsiveness of the enzyme was depressed throughout the entire period. After 12 weeks, which was the time of cessation of the diet and of the appearance of the first tumors, the isoproterenol response decreased but never fell below normal levels. At this time also, the basal activity and fluoride response fell to below control levels; the glucagon response remained depressed. Hormone responsiveness of cyclase from established tumors was variable but never high; basal activity was always low. It is concluded that enhanced basal activity and the appearance of more effective β-adrenergic stimulation of adenyl cyclase may be related to neoplastic transformation but not to the uncontrolled growth of established tumors.