Action of Caffeine in Altering the Carcinogen-Activating and -Detoxifying Enzymes in Mice.

Abstract

SummaryCaffeine through drinking water, at low (100 p g/ml), moderate (200 and 400 1u g/ml) and high (800 p g/ml) doses, as well as by intragastric administration at 40 and 160 mg/kg doses, increased the hepatic and pulmonary cytochrome P-450 (Cyt. P-450) levels in mice. The extent of elevation in the enzyme levels was dependent on the dose of caffeine. Maximum inducibility of hepatic arylhydrocarbon hydroxylase (AHH) was observed at the highest doses of caffeine by the two modes of treatment. However, the activities of AHH at the highest doses were not statistically different from the enzyme activities at the lowest doses. Caffeine treatment of animals through drinking water did not change the pulmonary AHH activity, whereas the intragastric administration of caffeine increased the enzyme activity in the lungs. Moreover, intragastric administration was more effective in inducing the hepatic AHH activity. Maximum increases in hepatic and pulmonary glutathione-S-transferase (GST), and in hepatic reduced glutathione (GSH), by the two modes of caffeine treatment of the animals was similar. The enhancement in AHH, Cyt. P-450, GST, and GSH may account for the anticarcinogenic activity of caffeine.Key Words: caffeine, arylhydrocarbon hydroxylase, cytochrome P-450, glutathione-S-transferase, reduced glutathione Environmental pollutants, several drugs, and nutritional factors are likely to have impact on the process of carcinogenesis. Caffeine, which is the most widely consumed drug throughout the world, is a natural ingredient of coffee, tea, cocoa and an additive to many medications and beverages, such as soft drinks and diet aids [1]. The pharmacological and pathological activities of caffeine have received

Anticarcinogenic Factors in Plant Foods: A New Class of Nutrients?

“…There are many examples of drugs and xenobiotics (Forrester et al 1992), including caffeine (Gandhi & Khanduja, 1992) and ethanol (Lucas et al 1992), which increase some P450 involved in phase I metabolism. Other non-nutrient components of human foods which have been shown to have this effect include the flavonoids tangeretin, flavone and nobiletin .…”

Dietary caffeine reduces the genotoxicity of MeIQx in the host‐mediated assay in mice

“…Furthermore caffeine is known to alter the spectrum of hepatic microsomal enzymes (19)(20)(21). For example, in mice, administration of caffeine in drinking water or by gavage resulted in significant increases in activity of cytochrome P-450, in particular, arylhydrocarbon hydroxylase (21). In addition, caffeine consumption was associated with increases (up to 2-fold) in hepatic factors, such as glutathione and glutathione transferase activity, associated with detoxification of carcinogens (21).…”

“…For example, in mice, administration of caffeine in drinking water or by gavage resulted in significant increases in activity of cytochrome P-450, in particular, arylhydrocarbon hydroxylase (21). In addition, caffeine consumption was associated with increases (up to 2-fold) in hepatic factors, such as glutathione and glutathione transferase activity, associated with detoxification of carcinogens (21). Thus it is possible that caffeine can alter the balance of enzymes and cofactors in the liver responsible for activation and detoxification of MelQx.…”

“…Caffeine is a substrate for CYP1A2, which catalyzes the major route of metabolism of MelQx, leading to genotoxic and carcinogenic metabolites in rats and humans (30,31). Furthermore caffeine is known to alter the spectrum of hepatic microsomal enzymes (19)(20)(21). For example, in mice, administration of caffeine in drinking water or by gavage resulted in significant increases in activity of cytochrome P-450, in particular, arylhydrocarbon hydroxylase (21).…”

“…Caffeine is of particular interest, because its own metabolism is, like MelQx, to some degree dependent on CYP1A2 (18). Treatment of animals with caffeine can induce cytochrome P-450 and phase II detoxifying enzymes in liver (19)(20)(21). Here, using the host-mediated assay (22), we describe the results of studies on the effect of dietary caffeine on the metabolism and genotoxicity of MelQx in vivo.…”