It has been hypothesized that generation of reactive estrogen-quinone species and oxidative stress, both of which result from the metabolic activation of estrogens, plays an important role in estrogen-induced carcinogenesis. In the present investigation, we used an estrogen-induced hamster renal tumor model to identify gene(s) associated with oxidative stress that may be differentially expressed in estrogen-induced tumors compared with untreated controls. Hamsters were implanted with 17beta-estradiol (E2) for 7 months. This treatment resulted in the development of target organ specific kidney tumors. Delta differential PCR technique on RNA isolated from estrogen-induced hamster renal tumors and untreated control kidneys identified a number of cDNA fragments that were differentially expressed in tumor RNA compared with untreated controls. We report the cloning of one of the differentially expressed cDNA fragments, the hamster calbindin-D28k (Cb28k) cDNA, and present a finding that both Cb28k mRNA and protein are suppressed in estrogen-induced hamster renal tumors compared with untreated controls. Cb28k is a Vitamin D3-dependent calcium binding protein that acts as a buffer to maintain intracellular calcium homeostasis, although its exact role is still not clear. Since Cb28k gene has been shown to be associated with providing cells resistance against oxidative stress, Cb28k may be an important biomarker in estrogen-mediated carcinogenesis and oxidative stress.