O6-Benzylguanine Enhances the In Vitro Immunotoxic Activity of Temozolomide on Natural or Antigen-Dependent Immunity

摘要: Temozolomide (TMZ) is a new cytotoxic triazene compound of clinical interest that able to generate methyl adducts at the O 6 -guanine DNA, which can be repaired by -alkylguanine-DNA alkyltransferase (OGAT). It was previously found compounds are highly immunosuppressive in mice. In present study, we investigate whether TMZ could affect immune functions human competent cells and methylation involved activity drug. Mononuclear (MNCs) obtained from peripheral blood healthy donors were tested for OGAT treated with alone or combined inhibitor -benzylguanine. Control drug-treated MNCs then assayed natural killer ability proliferate effector response interleukin-2 allogeneic MT-2 tumor cells. The results show inhibited both proliferation induction lytic Moreover, an inverse correlation between their sensitivity TMZ. involvement effects further confirmed finding -benzylguanine increased On other hand, only moderately affected TMZ, no relationship observed levels These data suggest patients tumors who undergoing treatment, drug may impair responses involving cell proliferation, depending on MNCs, potentiate this activity.