Metabolism of drugs and carcinogens in man: Antipyrine elimination as an indicator

Kalamegham, R.; Krishnaswamy, Kamala; Krishnamurthy, Sairam; Bhargava, Ravi

doi:10.1002/cpt197925167

Cited by 26 publications

(7 citation statements)

References 8 publications

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“…These results confirm those of our earlier study (Pelkonen et al, 1980) in which we showed that correlations between P-450, aryl hydrocarbon hydroxylase, 7-ethoxycoumarin O-deethylase and parameters of antipyrine elimination, although statistically significant, were not good enough for predictive purposes. Similar findings have been published by Kapitulnik et al (1977) and Kalamegham et al (1979).…”

Section: /[S]supporting

confidence: 92%

Coumarin 7‐hydroxylase activity in human liver microsomes. Properties of the enzyme and interspecies comparisons.

Pelkonen¹,

Ea²,

Ahokas³

1985

Brit J Clinical Pharma

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Coumarin 7‐hydroxylation and other cytochrome P‐450‐associated enzyme activities were studied in human liver biopsy homogenates and compared with activities in livers of other species. Coumarin 7‐hydroxylation is extraordinarily active in human liver biopsy samples in vitro. Activity is lower in mouse, rabbit or guinea pig liver and essentially absent in rat liver. Cytochrome P‐450 content and other associated enzyme activities were higher in animals. Coumarin 7‐hydroxylation is induced by phenobarbitone in mouse liver, but no significant increase was seen in human or rat liver after exposure to inducers. Correlations amongst coumarin 7‐hydroxylase, aryl hydrocarbon hydroxylase, 7‐ethoxycoumarin O‐deethylase and cytochrome P‐450 are statistically significant (r values from 0.56 to 0.73), but do not permit the conclusion, that the same P‐450 form catalyzes all the reactions studied. The correlations between coumarin hydroxylation and antipyrine half‐life or clearance are statistically significant, but not good enough for predictive purposes. Coumarin 7‐hydroxylase in human liver is inhibited by alpha‐ naphthoflavone, SKF 525A, metyrapone and aniline.

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Section: /[S]supporting

confidence: 92%

Coumarin 7‐hydroxylase activity in human liver microsomes. Properties of the enzyme and interspecies comparisons.

Pelkonen¹,

Ea²,

Ahokas³

1985

Brit J Clinical Pharma

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“…The total cytochrome P450 content was measured according to Omura and Sato [19] in S10 mix prepared from control, PCB and PB plus BNF-treated animals. The enzymatic activity was determined according to Kalameghan et al [20], using a 8 mM antipyrine as substrate and measuring HCHO production expressed as g of formaldehyde (HCHO) generated per mg protein per 20 min. S10 mix cofactors were: 80 mM MgCl 2 ; 330 mM KCl; 50 mM glucose-6-phosphate; 40 mM NADP, pH 7.4.…”

Section: Induction Of Microsomal Enzyme Activitymentioning

confidence: 99%

Histamine release from rat mast cells induced by the metabolic activation of drugs of abuse into free radicals

Bello¹,

Masini²,

Ioannides

et al. 1998

Inflamm. res.

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“…The first such study (Kellermann et al, 1973a, b), widely cited, reported that high and intermediate AHH inducers, 9% and 46% of the population, had 37 and 16 times respectively the lung cancer risk of low inducers (45% of the population). Subsequent studies did not reproduce these results, but some later studies have also reported higher AHH inducibility in lung cancer cases than controls, and of all the studies (Table III) (Jett et al, 1979) and there was no significant difference in the other (Rudiger et al, 1980 Kalamegham et al (1979) in biopsied liver (r = -0.52) and by Atlas et al (1976) and Boobis et al (1981) measuring AHH inducibility in cultured lymphocytes (r= -0.55 and r = -0.84). With hindsight AP was not an appropriate choice as a potential marker drug.…”

Section: Phase II Conjugationmentioning

confidence: 95%

Genetic predisposition to lung cancer

1990

Br J Cancer

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In Britain, the life-time risk of lung cancer in men who smoke 20 or more cigarettes per day is about 15%. That most smokers never develop lung cancer has promoted interest in the role of host factors. While chance, other environmental factors and the competing effect of other diseases, some of which are also smoking related, are all likely to affect individual lung cancer risk, genetic factors may also be important. This review examines the evidence for genetic predisposition to smoking related lung cancer.The review concentrates on the numerous metabolic studies that have sought differences between individuals in the genetic control of biochemical pathways that could be involved in the metabolism of carcinogens in tobacco smoke. Insights gained are likely to have wider implications for other environmental carcinogens. Other studies that have sought simple evidence, such as familial clustering or associations of lung cancer with blood group, HLA and other naturally occurring antigens, are also examined. The field of chromosomal abnormalities in lung cancer and the difficulties in interpreting them is reviewed only briefly, since this area may not directly relate to tobacco smoking and has been reviewed elsewhere (Birrer & Minna, 1988). Various sources of bias important in the interpretation of the metabolic studies in particular are outlined. Future research is likely to be dominated by the recent advances in molecular genetics that offer the possibility of circumventing bias by the direct identification of genes, but at present this is possible only to a limited extent. Familial clustering of lung cancer casesFamilial clustering of a cancer (or indeed of any disease) is an insensitive indicator of genetic predisposition. Peto (1980) and Bodmer (1986) have pointed out that a cancer can have a major genetic component yet show no detectable familial clustering. The ratio of the incidence of the cancer in relatives of known cases to that in age-matched controls is the only measure of familial clustering (in the absence of a marker). This ratio will be much smaller than the ratio of the incidence in genetically susceptible to non-susceptible individuals, which is the direct measure of the magnitude of the genetic effect. It is a question of dilution -not all patients with cancer will be genetically susceptible individuals, fewer of their relatives will be, and tne general population contains susceptibles as well as non-susceptibles. (1980) showed that even with a very large cancer risk in susceptibles, the incidence of cancer in relatives will generally be increased by no more than 1.5-3-fold. It is difficult in a family study to show that such a modest increase could not be due to chance, shared exposure or other bias.Five studies have examined lung cancer incidence in relatives of cases, but three (Tokuhata & Lilienfeld, 1963b;

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Metabolism of drugs and carcinogens in man: Antipyrine elimination as an indicator

Cited by 26 publications

References 8 publications

Coumarin 7‐hydroxylase activity in human liver microsomes. Properties of the enzyme and interspecies comparisons.

Coumarin 7‐hydroxylase activity in human liver microsomes. Properties of the enzyme and interspecies comparisons.

Histamine release from rat mast cells induced by the metabolic activation of drugs of abuse into free radicals

Genetic predisposition to lung cancer

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