Radiation-induced cell transformation: transformation efficiencies of different types of ionizing radiation and molecular changes in radiation transformants and tumor cell lines.

This study aims to compare the efficiencies of 5.4 keV soft X-rays, alpha-particles, and gamma-rays in transforming C3H 10T1/2 cells and to assess the sequence of cellular and molecular changes during the process of radiation-induced transformation of Syrian hamster embryo (SHE) cells. The somewhat more densely ionizing soft X-rays are more effective than gamma-rays both for cell inactivation and cell transformation. The relative biological effectiveness (RBE) appears to be independent of dose; it is approximately 1.3 for either end point. The RBE of alpha-particles versus gamma-rays, on the other hand, increases with decreasing dose; the dose dependence is somewhat more apparent for cell transformation than for cell inactivation. SHE cells transformed by different types of ionizing radiation and related tumor cell lines isolated from nude mice tumors were found to have a distinct growth advantage compared to primary SHE cells, documented by higher plating efficiencies, shorter doubling times, and higher cloning efficiencies in semisolid medium. Most transformed and tumor cell lines that were investigated have elevated mRNA levels for the H-ras gene, some of them show restriction fragment length polymorphisms of the H-ras gene, and some exhibit a substantially amplified c-myc gene. In a sequence analysis of the Syrian hamster H-ras gene of eight tumor cell lines from radiation transformants, we have not found any mutation in codons 12, 13, 59, 61, nor in the flanking regions of these codons. The transformed and tumor cell lines tend to have lower chromosome numbers than primary SHE cells.

Neoplastic transformation of mouse C3H 10T1/2 and Syrian hamster embryo cells by heavy ions.

C3H 10T1/2 mouse-embryo fibroblasts were used for transformation experiments to study the effectiveness of various heavy ions with energies up to 20 MeV/u and LET values from 170 to 16,000 keV/micrometers. The transformation frequency per unit absorbed dose decreased with increasing ionization density; at the highest values of LET we found a decrease even of the transformation efficiency per unit fluence. Uranium ions at energies of 5, 9, and 16.3 MeV/u did not induce any transformation. In additional studies primary Syrian hamster embryo cells (SHE) were exposed to heavy ions in order to characterize cytological and molecular changes which may be correlated with neoplastic transformation. Growth behaviour, chromosomal status, tumorigenicity in nude mice, and expression of oncogenes of transformed cell lines were examined