Carcinogenesis, Vol. 20, No. 7, 1331-1336,
July 1999
© 1999 Oxford University Press
Carcinogenesis |
Smoking disturbs mitochondrial respiratory chain function and enhances lipid peroxidation on human circulating lymphocytes
Muscle Research Unit, Department of Internal Medicine, `August Pi i Sunyer' Biomedical Research Institute (IDIBAPS), Hospital Clínic Medical School, University of Barcelona, Villarroel 170, 08036 Barcelona, Catalonia, Spain
Mitochondria constitute a source of reactive oxygen species. We tested whether mitochondrial function from human circulating lymphocytes is affected by smoking habit and if this could be associated with an increase in oxidative damage of biological membranes. We prospectively studied 35 smokers and 35 non-smoking healthy individuals matched by age and sex, with a similar physical activity. Individual enzyme activity of complexes II, III and IV of the mitochondrial respiratory chain (MRC) and of glycerol-3-phosphate dehydrogenase activity were measured spectrophotometrically. Intact cell respiration and oxidative rates after addition of pyruvate, succinate and glycerol-3-phosphate were assessed polarographically. Lipid peroxidation of biological membranes was assessed measuring the loss of cis-parinaric acid fluorescence. Results are expressed as means (±SD). Smokers showed a significant decrease in complex IV activity compared with non-smokers (112.8 ± 40.9 versus 146.4 ± 62.5 nmol/min/mg protein, respectively; 23% of inhibition; P = 0.01), while the rest of the complexes of MRC were unaffected. Conversely, oxidative rate with succinate, but not with the other substrates, was enhanced in smokers compared with non-smokers (16.7 ± 10.4 versus 11.4 ± 4.7 nmol oxygen/min/mg protein, respectively; 46% of activation; P = 0.01). Lipid peroxidation of lymphocyte membranes was increased in smokers with respect to non-smokers (3.49 ± 1.27 versus 4.39 ± 1.76 units of fluorescence/mg protein, respectively; 21% of increase; P = 0.03) and this increase correlated positively with succinate oxidation activation (R = 0.34, P = 0.02) and, to a lesser extent, with complex IV inhibition, although it did not reach statistical significance (R = 0.19, P = 0.18). In smokers, the MRC function of lymphocytes is disturbed and correlates with the degree of oxidative damage of membranes. This mitochondrial dysfunction could contribute to increased endogenous production of reactive oxygen species and could play a role in tobacco carcinogenicity.
Abbreviations: CO, carbon monoxide; COHb, carboxyhemoglobin; MRC, mitochondrial respiratory chain; ROS, reactive oxygen species.
1 To whom correspondence should be addressed Email:cardell{at}medicina.ub.es
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