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Publisher Summary This chapter examines the reactions of carcinogens with sulfhydryl group (SH) groups in vivo and in vitro. Normal cell division and growth have been found to be associated in some organisms with a SH-SS cycle, which can be modified by SH compounds and certain SH-reacting substances. The chapter also discusses the de novo synthesis of glutathione (GSH) and certain SH containing acid-soluble materials during the SH-SS cycle. Because growth inhibition is a characteristic property of certain carcinogens, both growth inhibition and the interaction between carcinogens and SH groups are discussed in the chapter in relation to systems associated with cell division and growth. The carcinogenic process may occur in three stages: (1) the inhibition of cell division through the interaction of carcinogen with critical SH groups, (2) an over compensatory response to the inhibition of cell division, and (3) a subsequent and permanent loss of control of cell division. This sequence of events could occur by feedback adjustment after the initial reaction of carcinogens with particular SH compounds. Physical and chemical carcinogens under certain conditions markedly inhibit the growth of animals, tumors, and cells. It is possible that these effects may be due to the interference with SH functions in the control of cell division. The growth-inhibitory action of the carcinogenic polycyclic aromatic hydrocarbons may result (1) from a general systemic suppression of GSH synthesis by a direct action of the carcinogens on GSH synthetases or on some other point in the synthesis of GSH, or (2) from an interference in the hormonal control of GSH synthesis for the whole body, in which process growth hormone may play some key part. Carcinogenic hydrocarbons have growth-stimulatory effects that, in general, arc not found in noncarcinogenic substances. |
