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Variation of microsomal mixed function oxidase(s) and human lung cancer

โœ Scribed by Gottfried Kellermann; James R. Jett; Mieke Luyten-Kellermann; Harold L. Moses; Robert S. Fontana


Book ID
101328052
Publisher
John Wiley and Sons
Year
1980
Tongue
English
Weight
482 KB
Volume
45
Category
Article
ISSN
0008-543X

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โœฆ Synopsis


Animal and human studies on aryl hydrocarbon hydroxylase (AHH) have demonstrated wide interindividual 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 halflives 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 < 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 > 0.05). The data support the previous observation that lung cancer patients have increased oxidation rates which, in addition to smoking, might have predisposed them to developing lung cancer.

Cancer 451438-1442, 1980.

RYL HYDROCARBON HYDROXYLASE (AHH), one of

A the microsomal mixed function mono-oxygenases, has been implicated in the formation of reactive metabolites from pol yc yclic aromatic hydrocarbons. 10;24,m This enzyme system has been studied extensively in animals1~25,28 and to a lesser degree in human tiss u e ~. ~, ~~~~" , ~~, ~~ Both animal and human studies have demonstrated wide interindividual variation in the activity and inducibility of AHH that appeared to be under genetic control. 16*30 First attempts to link this variation to the susceptibility to certain cancers have been successful in mice2' but have remained inconclusive in human ~~b j e ~t ~. ~~~~' ~* ~~~~~

The main reason for the conflicting results seemed to be the use of mitogenstimulated lymphocytes that gave highly reproducible AHH results in 50me subjects but quite variable results in others. In addition, the lymphocytes of certain cancer patients showed a decreased response to the stimulation by phytohemagglutinin and pokeweed, which makes this test system unsuitable for the assessment of individual AHH activity in cancer pa-From the


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