Study on the Relationship Between Depletion of O~6-Methylguanine-DNA Methyltransferase and Cancer Chemotherapy

Drug resistance is still one of the major problems in cancer therapy. However, during the past several years, many efforts have been focused on reversing or depleting the molecular basis of drug resistance along with the elucidating of the mechanisms involved.Nitrosourea compounds such as 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) and 1, 3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) are an important class of useful antitumor drugs. They exert their antitumor activity by alkylating the O~6 position of guanine and leading to a DNA interstrand cross-link. Introcellular O~6-methylguanine-DNA methyltransferase (O~6-MT) can repair the mentioned DNA lesions and thus plays an important role in determining the sensitivity of tumor