Genetic and Environmental Factors Affecting Host Response to Drugs and Other Chemical Compounds in Our Environment

Vesell, Elliot S.; Passananti, G. Thomas

doi:10.2307/3428654

Cited by 3 publications

(2 citation statements)

References 26 publications

(29 reference statements)

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“…The rationale for this latter measurement was the following: first, as shown previously with in vitro systems, the putative carcinogens in opium pyrolysates require metabolic activation to exert genetic effects Hewer et al, 1978;Malaveille et al, 1982). Individual susceptibility might then be reflected in drug-metabolizing capacity (Conney et al, 1976;Vessel and Passananti, 1977;Kalamegham et al, 1979). Second, the role of diet might be exerted through its effect on the metabolism of carcinogenic substances (Conney et al, 1977).…”

mentioning

confidence: 99%

Oesophageal cancer studies in the caspian littoral of Iran: Some residual results, including opium use as a risk factor

Ghadirian¹,

Stein

Gorodetzky

et al. 1985

Intl Journal of Cancer

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A study was conducted in northern Iran in areas of very high, high and moderately low incidence of oesophageal cancer. Morphine metabolites in urine as an indicator of opium use, and a variety of nutritional and biochemical measures, including salivary antipyrine half-life, were determined in households with a case of oesophageal cancer and in control households. Results on 1,590 individuals showed that the prevalence of appreciable levels (greater than or equal to 1 microgram/ml) of urinary morphine metabolites was much higher in areas of high and very high incidence of oesophageal cancer than in low-incidence areas, particularly for those under age 50 years in both sexes, where a 6-fold difference was seen. Members of households with a case of oesophageal cancer had a higher prevalence of positive urinary morphine metabolite findings than members of control households from the same village. Salivary anti-pyrine half-life (AP-T1/2), as a measure of hepatic drug metabolizing capacity, was estimated in 120 subjects. No relationship was seen with use of opium, region of residence, case-control status of household, age or sex. Experimental studies have meanwhile identified mutagenic substances with carcinogenic potential in opium pipe scrapings, used widely in the study region, opium pyrolysates and morphine pyrolysates. Our data give additional support to the hypothesis that opium use, in the form of its pyrolysates, is one of the factors involved in the aetiology of oesophageal cancer in the region.

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mentioning

confidence: 99%

Oesophageal cancer studies in the caspian littoral of Iran: Some residual results, including opium use as a risk factor

Ghadirian¹,

Stein

Gorodetzky

et al. 1985

Intl Journal of Cancer

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“…Adults usually exhibit large interindividual differences in their ability to metabolise drugs (Vesell 1977;Vesell & Passananti 1977). These differences, which may be due to genetic and/or environmental factors (Mucklow 1988;Nebert et al 1981;Nebert & Bigelow 1982), most probably contribute to the various degrees of drug-induced toxicities.…”

Section: Fetal and Neonatal Versus Adult Drug Metabolismmentioning

confidence: 99%

Fetal Drug Metabolism and Its Possible Clinical Implications

Krauer

Dayer

1991

Clinical Pharmacokinetics

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The ability of the human conceptus to metabolise xenobiotics during early gestation is now well established. Specific activities of liver enzymes have been demonstrated to exist in the late embryonic phase for numerous cytochrome P450 monooxygenases and many phase II enzymes such as glutathione-, N-acetyl-, sulpho- and uridine diphosphate-glucuronosyltransferase. As in the adult, fetal drug metabolism may function in a dual manner, either as a protective mechanism against chemical aggression when transforming active molecules into inactive ones, or as a toxifying system when transforming innocuous compounds into reactive metabolites. Recent advances in the understanding of enzyme variabilities at molecular and functional levels illustrate the necessity of studying these variations in the human fetus as well as in adults, since the combination of genetic, developmental and environmental factors seem to control fetal enzyme activities and ultimately determine the variability in individual susceptibility to chemicals in utero. Despite the scarcity of well documented cases of adverse fetal reactions resulting directly from metabolic toxicity, the clinical relevance of the potential role of biotransformation in generating fetal toxicity is a strong appeal to promote further studies dealing with the ontogeny of drug-metabolising capacity and its regulation.

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Drug metabolism in alcoholics

Pelkonen

Sotaniemi

1982

Pharmacology & Therapeutics

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Genetic and Environmental Factors Affecting Host Response to Drugs and Other Chemical Compounds in Our Environment

Cited by 3 publications

References 26 publications

Oesophageal cancer studies in the caspian littoral of Iran: Some residual results, including opium use as a risk factor

Oesophageal cancer studies in the caspian littoral of Iran: Some residual results, including opium use as a risk factor

Fetal Drug Metabolism and Its Possible Clinical Implications

Drug metabolism in alcoholics

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