Radiation-induced malignant transformation develops by a stepwise accumulation of molecular changes including mutation, amplification or overexpression of certain genes. Amplification and/or overexpression of mdm2 may be one of several molecular mechanisms for an altered growth control leading to the transformed phenotype. In the present investigation, we examined amplification, level of expression as well as mutation of mdm2 in radiation-transformed mouse C3H 10T1/2 cell clones. None of the clones examined showed structural changes of the mdm2 gene. However, mdm2 was amplified in 8 of 30 and overexpressed in 3 of 11 independent X-ray (600 cGy) transformed 10T1/2 cell clones, as compared with nontransformed, control or ultraviolet light (UVL)-transformed clones. None of the clones showing amplification and overexpression of mdm2 were among the 9 with alterations in the p53 gene. These results suggest that although amplification of the mdm2 gene may play a role in the transformation of some 10T1/2 cells, radiation-induced malignant transformation probably arises as a consequence of genetic events that involve several different pathways.

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