THE importance of certain thiols and disulphides as protective agents against the lethal effects of ionizing radiation, and certain alkylating agents such as nitrogen mustards is well known. Two of the most effective radiation protection agents are cysteine and cysteamine.The amino acid cysteine occurs in the body in both the free and combined forms. Free cysteine occurs in the free state in equilibrium with the disulphide cystine, and in combination in such diverse molecular species as glutathione, proteins and enzymes. The sulphydryl groups present in molecules involved in intra-cellular metabolism have several functions, notably, participation in enzymic activity, regulation of the oxidation-reduction potential and in determining the degree of folding and coiling in the tertiary structure of enzyme and protein molecules.In a study of the chemical aspects of carcinogenesis, Tonge (1962) had reported the effect of tobacco smoke condensate on the aerial oxidation of cysteine. Evidence was produced supporting the presence of trapped free-radicals in tobacco smoke condensate. Lange (1961) has shown that two SH containing enzymes, rabbit muscle glyceraldehyde-3-phosphate dehydrogenase and yeast alcohol dehydrogenase were irreversibly inhibited by tobacco smoke. The addition of a large excess of cysteine caused a partial enzymic reactivation and furthermore the inhibition did not occur with previously inhaled smoke. It was possible to explain these results by the presence of peroxide arising from the free radicals present in tobacco smoke condensate. Sato, Suzuki and Fukuyama (1962) have reported that the enzymes succinic dehydrogenase and urease could be inhibited by the water-soluble fraction of tobacco smoke; moreover, the inhibition could be reduced almost to zero by pre-incubating the tobacco smoke condensate with cysteine or glutathione. The process of inhibition was markedly decreased if the tobacco smoke solutions were left at 20°C. overnight before reaction with the enzymes. They also reported that both cysteine and glutathione reacted with the water-soluble fraction of tobacco smoke, but no reaction products were identified.In view therefore of the established relationship between excessive cigarette smoking and carcinoma of the bronchus it was decided to investigate the action of cigarette smoke on cysteine in more detail than hitherto.
A PREVIOUS communication (Braven, Bonker, Fenner and Tonge, 1967) described the experimental evidence for a specific reaction between acetaldehyde vapour in cigarette smoke and free cysteine. This reaction resulted in the elimination of cysteine with the formation of 2-methyl-L-thiazolidine-4-carboxylic acid.The known relationships between thiols and protection against mutagenic agents were reviewed and a " Thiol-defence " hypothesis to explain the aetiology of carcinoma of the bronchus by cigarette smoke was presented.The hypothesis.In its present form, specifically related to cigarette smoking, this hypothesis may be stated as follows:One of the causes of cancer of the bronchus may be the inhalation of compounds in cigarette smoke which are capable of reacting with thiols, thereby causing the removal of free cysteine from the cells of the bronchial epithelium. This removal might result in suppression of the protection against mutagenesis which is normally afforded by cysteine. but other cysteine-removing reactions are also significant. This suppression of a protective function might operate against a background either of direct chemical or physical carcinogens or a probability of mutagenesis inherent in chromosome structure.Such a hypothesis can, of course, be merely tentative and is stated in this way only in order to expose it to criticism.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.