Chromosome damage induced by high-LET alpha-particles in plateau-phase C3H 10T1/2 cells

Chromosome aberrations induced by X-rays and alpha-particles (LET = 177 keV/microns) were observed at the first mitosis in C3H 10T1/2 cells released from density-inhibited cultures. X-radiation induced more chromosome exchanges than breaks (71% vs 27% of total aberrations), while a predominance of breaks (63%) was observed after alpha-irradiation. A linear-quadratic dose-response relationship was obtained for X-rays, while that for alpha-particles was linear. The RBE values for total aberration induction (ranging from 5.1 at low doses to 4.4 at high doses) were very similar to the RBE for cell killing (from 5.2 to 4.3). The RBE for dicentric induction (approximately 2) was much lower than the RBE for the induction of both breaks (from 7 to 6) and interstitial deletions (from 9 to 7). This behaviour supports the hypothesis that chromosome deletions play a major role in the malignant transformation of 10T1/2 cells. A high correlation between cell killing and number of acentric fragments per cell was found. The number of acentrics/cell at the mean lethal dose was about 1.4. This number was reduced to 1.0 when asymmetrical interchanges, which generally result in very small deletions, were subtracted from acentrics. It could be hypothesized that very small deletions could not impair cell survival. However, an alternative hypothesis related to the aneuploid state of C3H 10T1/2 cells can be formulated. Robertsonian translocations were also observed at the first mitosis. The dose-response curve of these translocations appears to be very similar to the dose-response curve for induction of sister chromatid exchanges (observed at the second mitosis) reported by other authors studying the same cell line. This similarity could indicate a general mechanism of action of radiation on the process of recombination of genetic material.