Determination of plasma trace elements in tumor-bearing animals by proton-induced X-ray emission spectroscopy

Although altered levels of circulating essential trace elements are known t o accompany malignant disease, the lack of sensitivity of conventional dete ction methods has generally limited their study to clinical conditions invo lving extensive disease (i.e., significant tumor burden). As such, the appl ication of altered trace element levels as potential prognostic guides or a s response indicators subsequent to treatment has been of limited use. Duri ng this study, proton-induced X-ray emission spectroscopy was evaluated as a tool to determine trace element imbalances in a murine tumor model. Using plasma from C57B1/6 mice bearing the syngeneic Lewis lung carcinoma (LLCa) , levels of Fe, Cu, and Zn, as well as changes in the Cu / Zn ratio, were m easured in animals carrying an increasing primary tumor burden. The plasma levels of Fe, Cu, and Zn were found to decrease significantly 7 d following implants of LLCa cells with no significant change observed in the Cu/Zn ra tio. By d 21, however, an increase in the Cu/Zn ratio was found to accompan y increased growth of the LLCa tumor; the plasma levels of Cu had returned to normal levels, whereas both the Fe and Zn plasma levels remained lowered . Collectively, the results suggest that although a net change in individua l plasma trace element concentrations might not be accurately associated wi th tumor growth, a clear relationship was established between the Cu/Zn rat io and tumor size.