Induction of aryl hydrocarbon hydroxylase activity and pulmonary carcinoma

Gahmberg, Carl G.; Sekki, Akseli; Kosunen, Timo U.; Holsti, Lars R.; Mäkelä, O.

doi:10.1002/ijc.2910230305

Cited by 49 publications

(14 citation statements)

References 12 publications

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“…Similar results have been reported by others [15][16][17] and the important role of AHH in PAH-induced carcinogenesis has recently been emphasized [18].…”

Section: Introductionsupporting

confidence: 80%

Oral and Oropharyngeal Cancer, Aryl Hydrocarbon Hydroxylase Inducibility and Smoking

Andréasson¹,

Björlin²,

Laurell

et al. 1985

ORL

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In a series of 50 consecutive cases with oral or oropharyngeal malignancies, aryl hydrocarbon hydroxylase (AHH) inducibility and smoking habits were studied. 82% of the patients were smokers. The AHH levels were divided into high, intermediate and low groups and were correlated to a healthy control material also divided into the groups mentioned. A significant overrepresentation of patients with a high AHH level (p < 0.0005) as well as an underrepresentation of low AHH levels (p < 0.01) was found. Smokers with a high AHH level run a sixfold risk of developing cancer in this area and develop it earlier in life than people with low or intermediate AHH levels. Recurrences or secondary malignancies in the upper digestive tract or airways were substantially higher in the high AHH level group as compared to the other. A high AHH inducibility level thus is of both pathogenetic as well as prognostic importance in oral and/or oropharyngeal cancer.

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“…Similar results have been reported by others [15][16][17] and the important role of AHH in PAH-induced carcinogenesis has recently been emphasized [18].…”

Section: Introductionsupporting

confidence: 80%

Oral and Oropharyngeal Cancer, Aryl Hydrocarbon Hydroxylase Inducibility and Smoking

Andréasson¹,

Björlin²,

Laurell

et al. 1985

ORL

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“…This activity is usually referred to as aryl hydrocarbon hydroxylase activity (AHH) in the lung (Anttila et al 1991). Furthermore, a positive correlation has been reported between the incidence of lung cancer and the inducibility of AHH in human lymphocytes (Gahmberg 1979;Kellerman et al 1973;Kiyohara et al 1998). Certain alleles of the human CYP1A1 gene have been implicated both in lung cancer and in prostate cancer in Japan (Hayashi et al 1992;Murata et al 1998;Rojas et al 2000), but these observations have not been reproduced in studies on Caucasian populations where the indicated alleles appear at much lower frequencies.…”

Section: Pah Exposure In Humansmentioning

confidence: 99%

Cancer Risk Assessment, Indicators, and Guidelines for Polycyclic Aromatic Hydrocarbons in the Ambient Air

Boström¹,

Gerde²,

Hanberg³

et al. 2002

Environ Health Perspect

873

459

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“…Referring to the studies of Kellermann et al (33), they suggested a correlation between the AHH activity in pulmonary macrophages and AHH induction in lymphocytes in the same subject for non-smoking cancer patients (32). However, extensive studies by other investigators have failed to confirm a connection between AHH inducibility in lymphocytes and the risk of bronchogenic carcinoma development while some studies could reproduce these results to various extent (34)(35)(36)(37)(38)(39). One of the reasons for these confusing and contradictory results may be the fact that the attempted correlation was restricted to AHH whereas other MO forms and further enzymes such as EH and GST also contribute to the control of reactive metabolites of PAH.…”

Section: Introductionmentioning

confidence: 99%

Monooxygenase, epoxide hydrolase, and glutathione-S-transferase activities in human lung. Variation between groups of bronchogenic carcinoma and non-cancer patients and interindividual differences

Oesch¹,

Schmassmann

Ohnhaus³

et al. 1980

Carcinogenesis

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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 long. 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-deethylatlon 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 EM (substrate: benzo 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 nonsmokers (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 (13076 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 EM, 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 ret liver hepatoma preparations, where EHI 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 nondiseased areas of the same lung.

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Induction of aryl hydrocarbon hydroxylase activity and pulmonary carcinoma

Cited by 49 publications

References 12 publications

Oral and Oropharyngeal Cancer, Aryl Hydrocarbon Hydroxylase Inducibility and Smoking

Oral and Oropharyngeal Cancer, Aryl Hydrocarbon Hydroxylase Inducibility and Smoking

Cancer Risk Assessment, Indicators, and Guidelines for Polycyclic Aromatic Hydrocarbons in the Ambient Air

Monooxygenase, epoxide hydrolase, and glutathione-S-transferase activities in human lung. Variation between groups of bronchogenic carcinoma and non-cancer patients and interindividual differences

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