A strong correlation was found in a carefully selected homogenous population (n = 57) between antipyrine plasma half-life and the percent induction of aryl hydrocarbon hydroxylase by 3-methylcholanthrene in mitogen-stimulated lymphocytes from the same individual. The correlation coefficient of r = 0.923 indicates that antipyrine and benzo[a]pyrene share one or several common determinants that are responsible for the observed interindividual variation in the oxidation rates of the two compounds. When a heterogenous population (n = 80) was studied, the above correlation was not found (r = 0.425).
Animal and human studies on aryl hydrocarbon hydroxylase (AHH) have demonstrated wide inter-individual variation. First attempts to link this variation to the susceptibility to certain cancers have been successful in mice but remained inconclusive in man. In a new approach, saliva antipyrine half-lives and metabolic clearance rates have been used to assess individual rates of benzo]a]pyrene metabolism in human subjects. Saliva antipyrine half-lives and metabolic clearance rates have been measured in 57 patients with lung cancer, 90% of whom had quit smoking more than three months prior to the test, 57 cancer-free matched controls, and 59 healthy smoking controls. The mean antipyrine half-life was significantly shorter (P less than 0.001) in lung cancer patients when compared with the cancer-free matched control group, but differed little from that of the smoking group (P less than 0.05). The data support the previous observation than lung cancer patients have increased oxidation rates which, in addition to smoking, might have predisposed them to developing lung cancer.
The plasma elimination rates of phenacetin, acetanilide and theophylline have been determined in 32 healthy subjects in an effort to find drugs resembling in their metabolism the carcinogen benzo(a)pyrene. The plasma half-lives and metabolic clearance rates of the three drugs were correlated with the inducibilities of aryl hydrocarbon hydroxylase (AHH) in mitogen-stimulated lymphocytes and the plasma half-lives and metabolic clearance rates of antipyrine determined in previous studies. Statistically significant correlations were found between the half-lives and metabolic clearance rates of phenacetin, acetanilide and theophylline and the AHH ratios except for the metabolic clearance rates of phenacetin which did not correlate. The correlations of the three drugs with the half-lives and metabolic clearance rates of antipyrine were equally good. Of all the drugs tested thus far for similarity in metabolism to benzo(a)pyrene, antipyrine showed the best association followed closely by theophylline.
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