Radiation resistance in a melphalan-resistant subline of a rat mammary carcinoma

Journal Article · Mon Aug 01 04:00:00 EDT 1994 · Radiation Research

DOI:https://doi.org/10.2307/3578669· OSTI ID:70238

Lehnert, S; Vestergaard, J; Batist, G; Aloui-Jamali, M A ^[1]

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1. McGill Univ., Quebec (Canada)

A subline of a rat mammary carcinoma (MATB 13762), selected for resistance to melphalan, is cross-resistant to other alkylating drugs, to unrelated drugs and to ionizing radiation. The difference in radioresponse between the sensitive wild-type cell line and the melphalan- and radiation-resistant line (MLN{sup r}) is related to the size of the {alpha} component in the linear-quadratic model. Reduction of dose rate does not affect the response of MLN{sup r} cells but does increase survival for wild-type cells. MLN{sup r} cells have elevated levels of reduced glutathione (GSH) and overexpress redox enzymes glutathione-S-transferase and glutathione peroxidase. Modest depletion of GSH (to 50% of control) radiosensitizes MLN{sup r} cells but not wild-type cells. On the basis of the results of an excitation assay, growth delay and tumor control experiments, MATB MLN{sup r} tumors are also more radioresistant than wild-type cells when irradiated in situ. However, wild-type cells irradiated shortly after excision of the tumor are much more radioresistant than the same cells irradiated 24 h after excision or maintained in culture, and their response resembles that of MLN{sup r} cells irradiated under the same conditions. These results suggest that, in spite of some similarity between the in vivo and in vitro observations, intrinsic radioresistance is not the most important factor influencing the response of MLN{sup r} cells in vivo. 22 refs., 7 figs., 4 tabs.

• Sponsoring Organization: USDOE
• OSTI ID: 70238
• Journal Information: Radiation Research, Journal Name: Radiation Research Journal Issue: 2 Vol. 139; ISSN 0033-7587; ISSN RAREAE
• Country of Publication: United States
• Language: English

Related Subjects

56 BIOLOGY AND MEDICINE
APPLIED STUDIES
ALKYLATING AGENTS
BIOLOGICAL EFFECTS
CARCINOMAS
CELL CULTURES
ENZYME ACTIVITY
GLUTATHIONE
MAMMARY GLANDS
RADIOSENSITIVITY
RATS