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Mutatect: a mouse tumour model for detecting radiation-induced mutations in vivo
H C Birnboim1, D Wilkinson, J K Sandhu
1Ottawa Regional Cancer Centre, Ottawa, Canada. birnboim@uottawa.ca
Abstract:
A new mouse model (Mutatect) that permits detection of mutations at the hprt (hypoxanthine phosphoribosyltransferase) locus is described. It is highly sensitive to detection of mutants induced by clastogenic agents such as ionizing radiation. MN-11 cells are grown as a subcutaneous tumour in C57BL/6 mice for a period of 2 weeks, during which time they can be exposed to mutagenic treatments. Cells taken from the animal are cultured ex vivo and 6-thioguanine (6-TG)-resistant mutant clones can be readily identified and scored. This model system may have special utility for detecting multi-locus deletion events (chromosomal mutations) induced by high LET forms of radiation that might be encountered in space.
Insights
A new mouse model, Mutatect, efficiently detects mutations at the hypoxanthine phosphoribosyltransferase (hprt) locus. This highly sensitive system is valuable for assessing DNA damage from agents like ionizing radiation, particularly in space exploration.
Area of Science:
- Genetics
- Toxicology
- Radiation Biology
Background:
- The hypoxanthine phosphoribosyltransferase (hprt) locus is a common target for genotoxicity testing.
- Detecting mutations induced by various agents, including radiation, is crucial for risk assessment.
Purpose of the Study:
- To describe a novel mouse model, Mutatect, for sensitive detection of mutations at the hprt locus.
- To evaluate the utility of this model for assessing DNA damage induced by clastogenic agents.
Main Methods:
- MN-11 cells were grown as subcutaneous tumors in C57BL/6 mice for two weeks.
- Mice bearing tumors were exposed to mutagenic treatments.
- Cells were harvested and cultured ex vivo to identify 6-thioguanine (6-TG)-resistant mutant clones.
Main Results:
- The Mutatect model demonstrated high sensitivity in detecting mutants induced by ionizing radiation.
- The system effectively identified 6-thioguanine-resistant mutant clones.
- The model shows potential for detecting multi-locus deletion events.
Conclusions:
- The Mutatect mouse model provides a sensitive platform for detecting hprt mutations.
- This model is particularly useful for evaluating the mutagenic effects of clastogenic agents like ionizing radiation.
- Its utility may extend to detecting chromosomal mutations induced by high-LET radiation in space environments.