Characterization of the ionizing radiation-inducible gene O6-methylguanine DNA methyltransferase and its role in radiation responses .
Published: 2004
Language: eng
Number of pages: 118
Description: O6-methylguanine DNA methyltransferase (MGMT) is a critical cellular resistance factor against the mutagenic and cytotoxic effects of O6-methylguanine (O6meG) DNA lesions, and via their repair, confers resistance to alkylating agents including several chemotherapeutic drugs. This study investigates the regulation of MGMT by ionizing radiation (IR) and its potential functional role in radiation responses. The present work indicates that the role of MGMT in radiation responses does not involve its classic O6meG repair function. Expression and enzymatic activity analyses show that MGMT is up-regulated by IR over a range of 0.5 to 20 Gy with delayed and long-lasting kinetics in several cell lines  in vitro, and in all normal and malignant tissues examined  in vivo. This has implications for cancer patients receiving combination modality treatment, where the induction of MGMT by initial radiation therapy could result in altered sensitivity of the tumour or normal surrounding tissues to subsequent chemotherapy.
Notes: Adviser:  Katherine A. Vallis.

Thesis (M.Sc.)--University of Toronto, 2004.

Electronic version licensed for access by U. of T. users.

Source: Masters Abstracts International, Volume: 43-03, page: 0797.

MICR copy on microfiche (2 microfiches).