The relationship of host factors to the pathogenesis of chronic bronchitis and obstructive airway disease: lymphoblast aryl hydrocarbon hydroxylase.
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Biomedical subjects
Publications and source records attributed to S M Naseem.
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Aryl hydrocarbon hydroxylase (AHH) activity and inducibility were studied in the lymphoblasts of 47 asbestos workers and 31 control subjects. Mean inducibility (3-methylcholanthrene [MC]-or dibenz(a,h,)anthracene [DBA]-induced divided by basal enzyme activity) was greater in the occupationally exposed subjects than in the control subjects. The estimated estimated change in mean value (+/- SE) of MC inducibility was 0.88 +/- 0.21 (P less than 0.001), and that of DBA inducibility was 1.59 +/- 0.56 (P less than 0.01). Differences in inducibility values were particularly apparent in 12 pairs of spouses, in all of whom the inducibility values of the occupationally exposed subjects exceeded those of their spouses. The differences in inducibility of AHH resulted from increases in induced activity, not from any appreciable change in basal activities. They were independent of subject age, sex, smoking status, year of first exposure to asbestos, yield of lymphoblasts, or the rate of blastogenesis as measured by the incorporation of tritiated thymidine into nucleic acid. Increased AHH inducibility may bear some relation to the greatly increased risk of bronchogenic carcinoma in asbestos workers who smoke cigarettes.
Addition of insulin to cultured mouse plasma tumor cells (MPC-11) increases the entry of tritiated cyclic adenosine 3',5'-monophosphate (3H-cAMP). No increase of entry of N6-O2-dibutyryl adenosine 3',5' cyclic monophosphate (DBcAMP), 5' adenosine monophosphate (5' AMP) or adenosine was noted in the presence of insulin. The stimulation of cAMP transport by insulin was concentration dependent and inactivated insulin had no effect on nucleotide transport. Intracellular radioactivity after transport of cAMP was largely 5'AMP, while most of the extracellular radioactivity remained as cAMP after incubation.
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High-performance liquid chromatography (HPLC) was used to separate, identify, and quantitate the trichothecin mycotoxin, T-2 (4 beta,15-diacetoxy-3 aopha-hydroxy-8 alpha [3-methyl-butyryloxy]-12,13-epoxy delta 9-trichothecin), and its metabolites in plasma and urine samples from cynomolgus monkeys treated with the toxin. A 15-min gradient elution system was developed to separate and measure radiolabeled T-2 mycotoxin and its metabolites. The HPLC technique for separating T-2 and its metabolites was compared with thin-layer chromatography. Samples from the in vitro metabolism of T-2 by plasma and urine were included as controls and as a measure of the toxin's stability in biological samples. Within 5 min, 22% of the plasma radiolabeled T-2 toxin was detected as metabolites after an intravenous administration of [3H] T-2 toxin to cynomolgus monkeys. By 24 h post-exposure, there was no parent T-2 toxin detected in plasma or urine. T-2 tetraol was the major metabolite detected in the plasma and urine of monkeys. Other metabolites observed in urine up to 5 days after exposure were 3'OH-T-2 and 3'OH-HT-2. We conclude that T-2 toxin was rapidly metabolized to more polar metabolites, which were eliminated in urine.