Abstract
The therapeutic efficacy and side-effects of the anticancer drug cisplatin (cis-diaminodichloro platinum, CDDP) depend on interactions with various biological nucleophils. The antitumour activity of CDDP results from bifunctional platinum adducts with DNA. The binding of platinum to protein sulfhydryl groups (-SH) has been suggested to be responsible for the observed nephrotoxicity of CDDP. Glutathione (GSH) also plays a role in the resistance of normal and tumour cells to CDDP. Several -SH containing compounds have been used to reduce CDDP-induced cytotoxicity. Moreover, selenium (Se) prevents the nephrotoxicity of CDDP without reducing its antitumour activity in mice. The effectiveness of Se protection correlates well with higher levels of both Se and GSH in kidney tissues. On the other hand, there is ample evidence that the administration of Se augments lymphocyte functions such as antibody production in human subjects as well as in experimental animals, while opposite effects have been observed for Se depletion. We undertook the present work to test the possibility that the Se contents of circulating blood lymphocytes (CBL) might be affected by CDDP and that concurrent administration of N-acetyl cysteine (NAC), a GSH pro-drug, might modify such interaction.