Published in Cancer Detection and Prevention 1999; 23(5):422-427.

Modulation of 06-Methylguanine-DNA Methyltransferase-mediated 1-(4-Amino-2-Methyl-5-Pyrimidinyl)Methyl-3-(2-Chloroethyl)-3-Nitrosourea Resistance by Antisense RNA

Shou-Ping Ji and Yang-Pei Zhang

Institute of Blood Transfusion Medicine, Beijing, China

Address all correspondence and reprint requests to: Zhang Yang-Pei, Institute of Blood Transfusion Medicine, 27 Taiping Rd., Beijing, 100850 P.R. China.

ABSTRACT: Mer+ HeLa S3 tumor cells with high levels of 06-methylguanine-DNA methyltransferase (MGMT) gene expression were transduced by retroviral-mediated MGMT antisense RNA. The MGMT mRNA, MGMT protein, and MGMT activity in transduced cells were only 28.7%, 32.7%, and 39.1% of that in HeLa S3 cells, respectively. The transduced cells showed more sensitive to ACNU than HeLa 53 cells both in cell survival and in nude mice experiments. Pathologic examination confirmed that transduced grafts were killed by ACNU. Our results suggested that MGMT gene expression could be modulated by retroviral-mediated antisense RNA and that Mer+ tumor drug resistance to ACNU could be reversed by modulation of MGMT gene expression.

KEY WORDS: antisense RNA, drug resistance, gene expression, 0^(6)-methylguanine-DNA methyltransferase.