Gene transfer to suppress bone marrow alkylation sensitivity

Alkylating agents represent a highly cytotoxic class of chemotherapeutic co mpounds that are extremely effective anti-tumor agents. Unfortunately, alky lating agents damage both malignant and non-malignant tissues. Bone marrow is especially sensitive to damage by alkylating agent chemotherapy, and is a dose-limiting tissue when treating cancer patients. One strategy to overc ome bone marrow sensitivity to alkylating agent exposure involves gene tran sfer of the DNA repair protein O-6-ethylguanine DNA methyltransferase (O(6) MeG DNA MTase) into bone marrow cells. O(6)MeG DNA MTase is of particular i nterest because it functions to protect against the mutagenic, clastogenic and cytotoxic effects of many chemotherapeutic alkylating agents. By increa sing the O(6)MeG DNA MTase repair capacity of bone marrow cells, it is hope d that this tissue will become alkylation resistant, thereby increasing the therapeutic window for the selective destruction of malignant tissue. In t his review, the field of O(6)MeG DNA MTase gene transfer into bone marrow c ells will be summarized with an emphasis placed on strategies used for supp ressing the deleterious side effects of chemotherapeutic alkylating agent t reatment. (C) 2000 Elsevier Science B.V. All rights reserved.