ACTIVITIES OF CARCINOGEN METABOLIZING ENZYMES IN HEPATIC AND EXTRA HEPATIC TISSUES OF IRON-DEFICIENT RATS

The effect of iron deficiency on the activities of xenobiotic metaboli zing enzymes, both activating (Phase I) and conjugating (Phase II), wa s 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 p eriod of 6 weeks. Another group of rats, which received an iron-suffic ient diet, was used as the control. Hematological investigations on he moglobin, protoporphyrin/heme ratio, and serum iron confirmed the deve lopment of iron deficiency in the experimental group by 6 weeks. At th e end of the experimental period, microsomes and cytosolic preparation s were made from various tissues that are sites of drug metabolism, i. e., liver, kidneys, lungs, and intestinal mucosa. Activities of many e nzymes 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 transferas e 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 urid ine diphosphoglucuronyl transferase, a conjugating enzyme. were signif icantly decreased in iron deficiency. An impairment in detoxification of ingested xenobiotics is thus indicated in iron deficiency. This mig ht lead to the persistence of ingested compounds in the body without e limination, 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 car c inogenesis.