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Increased binding of benzo[a]pyrene metabolites to lymphocytes from patients with lung cancer
Abstract:
This study was performed to determine whether lymphocytes from individuals with lung cancer were more likely to bind benzo[a]pyrene (BP) metabolites in an in vitro test. The in vitro system consisted of peripheral blood lymphocytes incubated with increasing concentrations of [3H] benzo[a]pyrene in the presence of beta-naphthoflavone-induced rat liver microsomes and a NADPH-generating system. The radioactivity bound to a TCA-precipitate of the lymphocytes was determined. The apparent affinity (Km) and maximal binding (Vmax) of this binding were calculated from double reciprocal plots of the data. Seven patients with primary lung cancer (squamous cell carcinoma and undifferentiated small cell carcinoma), none of whom had smoked for at least 2 months, were studied as were 10 lung cancer free smokers, and the results compared with 13 age- and sex-matched controls. In lymphocytes from patients with primary lung cancer, Vmax of radiolabel bound to TCA-precipitable material was almost double that of non-smoking controls (205 +/- 19.2 pmol X 2h X 10(6) cells vs. 121 +/- 10.8 pmol X 2h X 10(6) cells, mean +/- S.E.M., P less than 0.01). Among individuals without lung cancer, smokers did not differ from non-smokers. In addition, there was no difference in Km of radiolabel binding to lymphocytes from patients in all 3 groups. It is concluded that binding of carcinogenic metabolites to cell components is increased in patients with lung cancer. Further studies are required to determine whether this increased binding is related to individual susceptibility of some smokers to lung cancer.