Monooxygenase, epoxide hydrolase, and glutathione-S-transferase activities in human lung. Variation between groups of bronchogenic carcinoma and non-cancer patients and interindividual differences
- 1 October 1980
- journal article
- research article
- Published by Oxford University Press (OUP) in Carcinogenesis: Integrative Cancer Research
- Vol. 1 (10), 827-835
- https://doi.org/10.1093/carcin/1.10.827
Abstract
Activities of microsomal monooxygenases (MO) and epoxide hydrolase (EH) and cytoplasmic glutathione-S-transferases (GST) will contribute to controlling the pool of reactive intermediates, enzymatically derived from polynuclear aromatic hydrocarbons (PAH) within the cells of target organs such as the human lung. Therefore, we studied what interindividual differences exist in these enzyme activities and whether there is a correlation between the activities of these epoxide forming and metabolizing enzymes in preparations from peripheral lung samples and the occurrence of bronchogenic carcinomas in smokers and non-smokers. 57 samples obtained from surgery were studied. Among them were 12 samples from non-smoking patients without cancer as a control group. It is not known whether this control group behaves, with respect to the investigated parameters, identically to fully healthy people, since in all cases indications existed which justified the removal of lung biopsies. Using very sensitive standard assays with benzo[a]pyrene, biphenyl, 7-ethoxyresorufin and 7-ethoxycoumarin as substrates, MO activity could only be determined as O-deethylation of 7-ethoxycoumarin and only after modification of the assay method. Evidence was obtained for the presence of a diffusible, but not dialyslble, MO Inhibitor in human lung microsomes. The MO activity (substrate: 7-ethoxycoumarin) in this fraction was extremely low in human (100-fold lower than in rat lung preparations), whereas EH (substrate: benzo[a]pyrene 4, 5-oxide) was slightly (about 2-fold) higher in human and GST (substrate: 2, 4-dinitrochlorobenzene) had similar activities in both species. Interindividual variations of enzyme activities in human lung were considerable: MO, 40-fold: EH, 5-fold; GST 10-fold. Compared to the control group (non-smokers without cancer) MO activities were slightly but significantly higher in lungs from bronchogenic carcinoma patients whether they were smokers (170% of controls, p < 0.0005) or non-smokers (320% of controls p < 0.025). MO activities of smokers without cancer were only very slightly elevated (140%) of controls, p < 0.05). Specific EH activities compared to the control group were slightly but significantly increased in smokers without cancer (160% of controls, p < 0.0125) and in bronchogenic carcinoma patients whether they used tobacco products (130% of controls, p < 0.005) or not (140% of controls, p < 0.05). Specific GST activities showed no significant differences (p > 0.1) between the various groups studied. The substrate specificity of human lung EH, which was studied using five K-region epoxides of various PAH as substrates, corresponded to that in human and rat liver and in human, mouse and rat skin and to the pure enzyme isolated from rat liver. In contrast to rat liver hepatoma preparations, where EH had been shown to be increased in the tumor tissue and had been identified as a preneoplastic antigen, EH activity in lung microsomal preparations from samples of peripheral squamous cell carcinomas of two subjects had in the tumor tissue only one third of the activity of non-diseased areas of the same lung.Keywords
This publication has 28 references indexed in Scilit:
- Hydration of arene and alkene oxides by epoxide hydrase in human liver microsomesClinical Pharmacology & Therapeutics, 1977
- ARYL-HYDROCARBON HYDROXYLASE-ACTIVITY IN PULMONARY MACROPHAGES AND LYMPHOCYTES FROM LUNG-CANCER AND NON-CANCER PATIENTS1977
- Interindividual Variation in Binding of Benzo[ a ]pyrene to DNA in Cultured Human BronchiScience, 1976
- Metabolism of benzo(a)pyrene and benzo (a)pyrene derivatives to mutagenic products by highly purified hepatic microsomal enzymes.Journal of Biological Chemistry, 1976
- The involvement of a diol‐epoxide in the metabolic activation of benzo(a)pyrene in human bronchial mucosa and in mouse skinInternational Journal of Cancer, 1976
- A rapid assay for epoxide hydratase activity with benzo(a)pyrene 4,5-(K-region-)oxide as substrateAnalytical Biochemistry, 1976
- Identification of mutagenic metabolites of benzo(a)pyrene in mammalian cells.Proceedings of the National Academy of Sciences, 1976
- GENETIC-CONTROL OF INTERINDIVIDUAL VARIATIONS IN INDUCIBILITY OF ARYL-HYDROCARBON HYDROXYLASE IN CULTURED HUMAN LYMPHOCYTES1976
- A fluorimetric study of the hydroxylation of biphenyl in vitro by liver preparations of various speciesBiochemical Journal, 1965
- PROTEIN MEASUREMENT WITH THE FOLIN PHENOL REAGENTJournal of Biological Chemistry, 1951