Elemental alteration, iron overloading and metallothionein induction in experimental hepatocarcinogenesis: a free radical-mediated process?

Abstract

The azo-dye p-dimethylaminoazobenzene (p-DAB) is a potential tumor initiator in rodents, but the underlying mechanism is not clear. Following chronic feeding of the carcinogen for 3, 5 and 7 weeks, trace elemental status, free radical generation, oxidative damage, antioxidant profile were measured in male and female swiss albino mice. The feeding resulted in iron accumulation in male mice liver. No increase in iron level was observed in similarly exposed female mice. The results of this study suggest that p-DAB-induced iron accumulation in male mice with concomitant production of oxidative free radicals is an early event in the hepatocarcinogenic initiation. This occurs selectively in male mice and affects either directly or indirectly in development of chemically induced liver neoplasia. Again, that upregulation of metallothionein (MT) expression in association with increased free radical generation was demonstrated in male mice. Alteration of copper (Cu) and zinc (Zn) levels are described in the light of antioxidant profile in liver tissue. The current results thus provide evidence in support of iron accumulations producing oxidative damage, and enhanced metallothionein expression as possible contributors in the mode of action of p-DAB induced hepatocarcinogenesis.