No abstract

A method for determining aryl hydrocarbon hydroxylase induction in human leukocytes is described. Leukocytes from healthy volunteers were cultured in the presence of phytohemagglutinin, a mitogen. Addition of 3-methylcholanthrene to 72-hour cultures induced a fourfold increase in aryl hydroxylase activity. In the absence of a mitogenic agent, 3-methylcholanthrene stimulation of increased enzymatic activity did not occur.

Aryl hydrocarbon hydroxylase (AHH) activity was measured in pulmonary alveolar macrophages (PAMs) and peripheral blood lymphocytes from cigarette smokers with and without primary lung cancer. Frequency distribution analysis of AHH induction ratios for the two groups revealed an increased number of individuals in the lung cancer patient group with high lymphocyte induction values (P less than 0.05). A similar increase was not shown for high-PAM AHH values in lung cancer patients (P greater than 0.2). When individual PAM and lymphocyte AHH values were compared between noncancer and lung cancer patients, a positive correlation was observed for noncancer patients (r=0.195, P less than 0.001), but no correlation of these values was noted for lung cancer patients. The lung cancer patients were divided into three subgroups of patients showing (I) high PAM and low lymphocyte AHH levels, (II) low PAM and low lymphocyte AHH levels, and (III) low PAM and high lymphocyte AHH levels. When the incidence of family history of cancer was compared for these subgroups, no family cancer history was recorded for persons in subgroup II; however, individuals in subgroups I and III presented family cancer history incidence of 9.5% and 39.3%, respectively. Patients in group III averaged 6 years younger than those in group I. These data suggest that familial factors may be identified among lung cancer patients and that these factors appear to associate as either a cause of an effect with the capacity of pulmonary alveolar macrophages and lymphocytes to be induced for AHH. The data support the hypothesis that high AHH values may be characteristic of lung cancer patients but show that enzyme values determined from a single tissue, either PAMs or lymphocytes, may not be appropriate for showing whether high AHH inducibility is correlated with lung cancer.

Aryl hydrocarbon hydroxylase (AHH) activity was measured fluorometrically in surgically-excised fresh lung tissue, pulmonary alveolar macrophages (PAMs), and peripheral blood lymphocytes from 14 cigarette smokers (7 with and 7 without primary lung cancer). Levels of AHH in fresh PAMs and AHH inducibility (expressed as fold-induction) in cultured, mitogen-stimulated lymphocytes from individual noncancer patients correlated well (r = 0.975, p < .001). For individual lung cancer patients, however, these values were dissociated (linear regression not appropriate for this set of values). Levels of AHH in fresh lung tissue and fold-induction ratios in cultured lymphocytes from individual noncancer patients also exhibited a positive correlation (r = 0.976, p < .001), while values for individual lung cancer patients did not (r = 0.007, p = 0.987). A close agreement was noted for AHH in fresh lung tissue a n d fresh PAMs from individual noncancer patients (r = 0.984, p < .001), while these values are weakly correlated for lung cancer patients (r = 0.658, p < .11). When AHH activity in fresh PAMs, in fresh lung tissue, and AHH inducibility in cultured lymphocytes were simultaneously compared, an excellent relationship was observed for values for all 3 tissues for individual noncancer patients (r = 0.987, p < .001). However, AHH levels in these 3 tissues from individual lung cancer patients were not correlated (r = 0.701, p > .25). These results indicate similar capacity for AHH induction is present in fresh lung tissue, fresh PAMs, and cultured mitogen-stimulated lymphocytes from cigarette smokers without evidence of lung cancer, but AHH values are not positively correlated with similar tissues from individual lung cancer patients.