Absence of seasonal variation in antipyrine metabolism.

The induced activity of aryl hydrocarbon hydroxylase (AHH), measured by the metabolism of benzo[a]pyrene to fluorescent products in cultured human lymphocytes, shows a strong seasonal variation. The in vivo metabolism of antipyrine, which is also catalyzed by microsomal cytochrome P-450-dependent monooxygenases, has been reported to be correlated with AHH inducibility in human lymphocytes. To determine whether antipyrine metabolism also showed seasonal changes, we measured antipyrine half-life (t 1/2) in 10 nonsmokers and eight smokers at the two times of the year that correspond to the high and low peaks of inducible AHH activity as measured in lymphocytes. The mean antipyrine t 1/2 determined in all 18 subjects in summer was almost identical to that found in winter (mean +/- SEM = 10.90 +/- 0.65 and 10.96 +/- 0.78 hr). AHH activity in cultured human lymphocytes from the nonsmoking subjects was determined in control and 3-methylcholanthrene-induced cells to obtained inducibility ratios of 4.2 +/- 0.56 (SEM) in the summer and 1.4 +/- 0.14 (SEM) in winter. These results indicate that the seasonal variation in AHH inducibility in human lymphocytes is not reflected by a corresponding seasonal variation in antipyrine metabolism in vivo

High-pressure liquid chromatographic analysis of benzo(a)pyrene metabolism by human lymphocytes from donors of different aryl hydrocarbon hydroxylase inducibility and antipyrine half-lives.

With high-pressure liquid chromatography (HPLC), lymphocytes from six human donors were evaluated for their ability to metabolize benzo(a)pyrene (BP). Donors whose aryl hydrocarbon hydroxylase (AHH) inducibility ratios ranged from 2.4 to 4.6 and whose antipyrine plasma half-lives ranged from 8 to 17 hr were examined. The BP metabolites identified were: 7,8-dihydrodiol, quinones, and 9-hydroxy and 3-hydroxy phenols. HPLC profiles of BP metabolites elaborated by uninduced (control) and benz(a)anthracene-induced lymphocytes were qualitatively similar among the six donors. A good correlation (r = 0.79) was found between known AHH inducibility ratios for the donors, as determined by the conventional fluorometric AHH assay, and induction of BP phenol production quantitated from HPLC data. HPLC results also indicated that the induction of benzo(a)pyrene-7,8-dihydrodiol, the proposed proximate carcinogenic form of BP, did not parallel BP phenol induction. Furthermore, the data also indicated a good negative correlation between AHH inducibility and the measurements of plasma antipyrine or urinary 4-hydroxyantipyrine half-lives (r = -0.88 or -0.91), respectively