Cigarette smoke-induced protein oxidation and proteolysis is exclusively caused by its tar phase: prevention by vitamin C

We have reported before that whole phase cigarette smoke (CS) contains stab le oxidants that cause oxidative damage and increased proteolysis of protei ns [Free Radic. Biol. Med. 27 (1999) 1064]. Here, we demonstrate that these oxidants are exclusively present in the tar phase of the CS and not its ga s phase and can almost wholly account for the observed whole phase CS-induc ed oxidation of human plasma proteins as well as extensive oxidative proteo lysis of guinea pig lung and heart microsomal proteins in vitro. The mechan ism of the tar phase CS-induced proteolysis of microsomal proteins involves two-steps: (i) initial oxidation of the proteins by oxidants present in th e tar extract followed by (ii) rapid proteolytic degradation of the oxidize d proteins by proteases present in the microsomes, Like the whole phase CS, the oxidative damage of proteins caused by the tar phase CS, as evidenced by the formation of protein carbonyl and bityrosine as well as loss of tryp tophan residues and thiol groups, is also almost completely prevented by as corbic acid and only partially by glutathione. Other antioxidants, includin g superoxide dismutase, catalase, vitamin E, beta -carotene and mannitol ar e ineffective. This again leads us to suggest that adequate intake of vitam in C may help smokers to evade the CS-induced degenerative diseases associa ted with oxidative damage. The revelation of the acute toxicity of the tar phase with respect to CS-induced oxidative damage also urges the necessity of trapping it more effectively by suitable cigarette filters to reduce the health damage caused to smokers. (C) 2001 Elsevier Science Ireland Ltd. Al l rights reserved.