PARENT SESSION
1:30 PM to 3:30 PM
Monday, April 22, 2002
Poster Session 9 Mutagenesis
Room: Nevada Exhibition Center

(P14-133) Suppression of radiation-induced germline mutations in mice by the adaptive response.

Somers, Christopher^*,1, Quinn, James¹, Boreham, Douglas², ¹ McMaster University, Department of Biology, Hamilton, Ontario (Canada)² McMaster University, Department of Physics and Astronomy, Hamilton, Ontario (Canada)

ABSTRACT-
Genotoxic effects in somatic cells caused by exposure to large doses of ionizing radiation can be reduced by a prior exposure to a small priming dose of radiation. This protective effect is believed to be a result of enhanced DNA repair capacity. This type of induced repair, termed adaptive response, has not been characterized for inherited mutations in mammalian germline cells. We have investigated the adaptive response and radiation-induced mutagenesis in rodent germ cells using DNA fingerprinting at hypervariable repetitive DNA loci. Mutations at these loci occur more frequently than at coding regions, reducing the sample size necessary to statistically compare mutation rates among different treatments. We exposed three groups of 8-12 week old male Swiss-Webster mice to high acute doses of cesium-137 gamma-radiation (0Gy, 0.5Gy, and 1.0Gy). A fourth group was exposed to an acute 0.1Gy priming dose 24 hours prior to an acute 1.0Gy dose. All males were held for 9 weeks, and then bred to unexposed females. We used mouse-specific multilocus probe MMS10 to create DNA fingerprint profiles for each pair of parents and 6 of their pups (pedigree analysis). Preliminary results show a 1.9x and 1.6x times elevation in inherited mutation frequency above the control group in pups from the 0.5Gy and 1.0Gy exposure groups, respectively. When males where adapted with a 0.1 Gy priming dose prior to the 1 Gy dose, there were fewer mutations than expected (only 1.1 times above control levels). These results show for the first time that the adaptive response can protect germline cells in mice from the mutagenic effects of large doses of radiation. We are currently expanding our study and performing additional genetic analysis to include mouse-specific single locus markers. These results support the contention that heritable genetic risk from exposure to ionizing radiation is not necessarily directly proportional to dose, and may be modified by inducible repair mechanisms.

KEYWORDS: germline mutation, adaptive response