Activities of Carcinogen Metabolizing Enzymes in Hepatic and Extra Hepatic Tissues of Iron-Deficient Rats.

Abstract

The effect of iron deficiency on the activities of xenobiotic metabolizing enzymes, both activating (Phase I) and conjugating (Phase II), was studied in an experimental system. A group of male weanling Fischer rats was fed a casein sucrose starch-based diet devoid of iron for a period of 6 weeks. Another group of rats, which received an iron-sufficient diet, was used as the control. Hematological investigations on hemoglobin, protoporphyrin/heme ratio, and serum iron confirmed the development of iron deficiency in the experimental group by 6 weeks. At the end of the experimental period, microsomes and cytosolic preparations were made from various tissues that are sites of drug metabolism, i.e., liver, kidneys, lungs, and intestinal mucosa. Activities of many enzymes of Phase I, like cytochrome P-450, aryl hydrocarbon hydroxylase, aminopyrine demethylase, aniline hydroxylase and microsomal epoxide hydrolase and of Phase II, like uridine diphosphoglucuronyl transferase and glutathione-S-transferase, were investigated. The results showed that the activities of aminopyrine demethylase, aniline hydroxylase, and microsomal epoxide hydrolase among the activating enzymes and uridine diphosphoglucuronyl transferase, a conjugating enzyme, were significantly decreased in iron deficiency. An impairment in detoxification of ingested xenobiotics is thus indicated in iron deficiency. This might lead to the persistence of ingested compounds in the body without elimination, which might prove to be harmful to the host. Formation of electrophilic metabolites without subsequent removal may result in the formation of DNA adducts, which is a necessary step in chemical carcinogenesis.