Altered copper absorption in tumor-bearing and estrogen-treated rats

Intestinal copper absorption was studied in normal, tumor-bearing and estrogen-treated rats, using 64Cu(NO3)2. Rats bearing Dunning mammary tumors (DMBA 5A) of more than 2 g absorbed 70-100% more of an intragastric copper dose than controls, and a much larger percentage was found in the plasma, with less in liver and kidney. The distribution of copper measured chemically mimicked these findings, and the enhanced capacity for absorption was also demonstrated in vitro with everted duodenal segments. Further examination of the intestinal mucosa revealed that binding of radioactive copper to a 10,000-dalton component of the cytosol was inversely proportional to the amount absorbed into the body, tumor-bearing rats retaining much less in, and transferring much more from, the intestine than controls. Daily injection of 17 beta-estradiol over 2 wk had the reverse effect. It is concluded that the absorption of copper is an endogenously regulated process that may be altered by cancer and estrogen treatment and mediated by the extent of its binding to a component (possibly metallothionein) within the mucosal cell.