PMID: 37562May 1, 1979

Biochemical evidence of cocarcinogenesis: tumor promoting agent enhances methylnitrosourea activation of rat guanylate cyclase activity

Research Communications in Chemical Pathology and Pharmacology
D L Vesely


The two-stage or cocarcinogenic hypothesis of carcinogenesis involves an initiator (carcinogen) and a promotor (cocarcinogen) being utilized in combination to produce more tumors than either would alone. This theory was tested at the cellular level utilizing Tumor Promoting Agent, 12-0-tetradecanoly-phorbol-13-acetate, (promotor) in combination with submaximal and maximal doses of methylnitrosourea (initiator). Tumor promoting agent, which can cause some tumors itself, was found to enhance the activity of guanylate cyclase (E.C., an enzyme that has been associated with normal and abnormal growth. Tumor promoting agent when utilized in combination with submaximal stimulatory doses of methylnitrosourea had an additive effect on guanylate cyclase activity, but the agent had no further additive effect on guanylate cyclase activation when methylnitrosourea was utilized in maximal stimulatory doses. These results indicate a carcinogen acting alone without a promoter can maximally activate guanylate cyclase and would suggest that at the cellular level a promotor is not absolutely necessary for the changes observed morphologically in canerous cells. The promotor, however, did enhance the enzyme's activity when a submaximal dos...Continue Reading

Related Concepts

Tumor Promoters
Nitrosourea Compounds
Guanylate Cyclase
Drug Augmentation
Phorbol Diesters
Drug or Chemical Tissue Distribution
Enzyme Activation

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