Release of lymphotoxin by control and chemical carcinogen-treated lymphocyte cultures derived from black healthy subjects and cancer patients.
In an age-adjusted comparison with white men, black men have a significantly higher increase in esophageal and other types of cancer associated with environmental causes. The basis of this increase in cancer rates in blacks over the last two decades is unknown. Since cancer patients generally show an impairment in cell-mediated immune (CMI) functions, we measured certain CMI reactions in cultured lymphocytes derived from black healthy subjects and cancer patients. We also determined the levels of aryl hydrocarbon hydroxylase (AHH) induced in these lymphocytes. AHH catalyzes the activation of polycyclic aromatic hydrocarbons (PAH) to intermediates which might alter CMI functions.Lymphocytes from 33 black patients with squamous cell carcinoma and 22 healthy volunteers were mitogen-activated with phytohemagglutinin and concurrently treated with the environmental carcinogen, 3-methylcholanthrene (MCA). Measurements were made of the effects of MCA (0.5 to 3.0 μM on blastogenesis, T-cell growth, lymphotoxin (LT) release, and AHH induction in these lymphocyte cultures. MCA treatment depressed blastogenesis but had no depressive effect on T-cell growth in cultures. Blastogenesis and T-cell growth were mitogen dose-dependent, while LT release was independent of mitogen concentration. There was a significantly lower LT release by lymphocytes from lung cancer patients, compared to those from healthy and head/neck cancer subjects. The reduced levels of LT release in lung cancer patients might reflect an impairment in this CMI function. Studies on the role of lymphocyte subpopulations in CMI functions are in progress.
D000328:Adult; D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000032:analysis; D044383:Black People; D002294:Carcinoma, Squamous Cell / Q000276:immunology; D006258:Head and Neck Neoplasms / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D008175:Lung Neoplasms / Q000276:immunology; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology*; D008233:Lymphotoxin-alpha / Q000378:metabolism*; D008748:Methylcholanthrene / Q000494:pharmacology*; D008875:Middle Aged; D009369:Neoplasms / Q000276:immunology*
D008233:Lymphotoxin-alpha; D008748:Methylcholanthrene; D001189:Aryl Hydrocarbon Hydroxylases