TRIPASS XR تري باس

 

Miller , J. A. & Miller, E. C. (l977a). The concept of reactive electrophilic metabolites in

chemieal carcinogenesis: Recent results with aromatie amines, safrole , and aflatoxin B,. In

BiologicalReactive Intermediates:Formation, Toxicity, and lnactivation, ed.Jollow, D. J.,

Kocsis, J. J., Snyder, R. & Vainio, H., pp. 6-24. New York: Plenum Press.

Miller, J. A. & Miller, E. C. (l977b). Ultimate ehemical earcinogens as reactive mutagenie

electrophiles. In Ortgins 0/ Human Cancer, Book B. Mechanisms 0/ Carcinogenesis,

ed. Hiatt, H. H., Watson, J. D. & Winsten, J. A., Cold Spring Harbor Conferences on Cell

Proliferation, vol. 4, Cold Spring Harbor Laboratory, Cold Spring Harbor, pp . 605-627.

Misra, P. S., Lefevre, A., Ishii, H., Rubin, E. & Lieber, C. S. (1971). Inerease of ethanol,

. meprobamate and pentobarbital metabolism after chronic ethanol administration in man

and in rats. Am. J. Med.,51, 346-351.

Monks, T. J., Caldwell , J. & Smith, R. L. (1979). Influence ofmethylxanthine-containing foods

on theophylline metabolism and kinetics . Clin. Pharmac. Ther., 26, 513-524 .

Pantuck, E. J., Hsiao , x.c., Conney, A. H., Garland, W. A., Kappas, A., Anderson, K. E. &

Alvares , A. P. (1976). Effect of charcoal-broiled beef on phenacetin metabolism in man.

Science, 194,1055-1057.

Pantuek, E. J., Hsiao, K.-C., Maggio, A., Nakamura, K., Kuntzrnan, R. & Conney, A. H. (1974).

Effect of cigarette smoking on phenacetin metabolism. Clin. Pharmac. Ther., 15, 9-17.

Pantuck, E. J., Kuntzman, R. & Conney, A. H. (1972). Decreased concentration ofphenaeetin

in plasma of cigarette smokers. Science, 175,1248-1250.

Pantuck, E. J., Pantuck, C. B., Garland, W. A., Min, B. H., Wattenberg, L. W., Anderson, K. E.,

Kappas, A. & Conney, A. H. (1979). Stimulatory effect ofbrussels sprouts and cabbage on

human drug metabolism. Clin. Pharmac. Ther., 25,88-95.

62 A. H. CONNEY. et al.

Poland, A., Smith, D., Kuntzman, R., Jacobson, M. & Conney, A. H. (1970). EfTect ofintensive

occupational exposure to DDT on phenylbutazone and cortisol metabolism in human

subjects. Clin. Pharmae. Ther.. 11,724-732.

Raaflaub, J. & Dubach , U. C. (1975). On the pharmacokinetics ofphenacetin in man. Eur. J.

clin. Pharmae.. 8,261-265.

Satterthwaite, F. E. (1946). An approximate distribution of estimates of variance components.

BiometriesBull.,2, 110-114.

Vesell, E. S. & Page, J. G. (1968). Genetic control of drug levels in man: Phenylbutazone.

Science, 159, 1479-1480.

Vesell, E. S. & Page, J. G. (1969). Genetic control of the phenobarbital-induced shortening of

plasma antipyrine half-lives in man. J. clin. Invest.. 48, 2202-2209.

Welch, R. M., Harrison , Y. E., Conney, A. H., Poppers, P. J. & Finster, M. (1968). Cigarette

smoking: Stimulatory efTect on metabolism of 3,4-benzpyrene by enzymes in human

placenta . Science, 160, 541-542.

Welch, R. M., Harrison, Y. E., Gommi, 8. W., Poppers, P. J., Finster, M. & Conney, A. H.

(1969). Stimulatory efTect of cigarette smoking on the hydroxylation of 3,4-benzpyrene and

the N-demethylation of 3-methyl-4-monomethylaminoazobenzene by enzymes in human

placenta. Clin. Pharmae. Ther.,10, 100-109.

Woolhouse, N. M., Andoh, 8. , Mahgoub, A., Sioan, T. P., Idle, J. R. & Smith, R. L. (1979).

Debrisoquine hydroxylation polymorphism among Ghanaians and Caucasians. Clin.

Pharmae. Ther., 26,584-591.

GENE-ENVIRONMENT

INTERACTIONS IN DRUG METABOLISM

E. S. VESELL

Departm ent 0/Pharm acology,

The Penn sylvania State University.

College ofMe dicine,

Hershey, Pennsylvan ia 17033. USA

Relationships among genetic and environmental factors that cause large variations

among normal subjects, as weil as among patients, in rates of drug elimination are

often discussed as though such factors were ent irely separate, unrelated entities

without interaction or interdependence. However, genetic and environmental factors

that control these large variations in rates of drug elimination interact dynam ically at

mult iple levels. In fact, to ach ieve expression genetic factors often require part icipation of environmental factors; and the latter often require a genetic apparatus to

exert their effects on drug dispostion . For example, the pharmacogenetic conditions

described and listed elsewhere (Table 2; Vesell, 1978) are expressed only in the

presenc e of an environmental agent: a drug . Toxicity then develops only in those

subjects whose genetic constitutions render them sensitive. The genetic factor may be

a metabolic block that leads to drug accumulation or it may consist of a structurally

altered receptor site that fails to bind the parent drug or its metabolites in anormal

way.