Mutagenic and chromosomal events in radiation transformation

The transformation of a normal cell to a cancer cell is a complex multi-stage process. Data are presented from rodent cells which suggest that the initial radiation induced change does not represent a mutation in a specific structural gene or group of genes. Rather, DNA damage induced by radiation produces a heritable change which leads to the transformation of one or more of the progeny of the initial irradiated cells at some later time. This second rare event has certain characteristics of a mutation. Studies in human diploid cells indicate that radiation induces stable chromosomal rearrangements which persist throughout the lifespan of the cells in culture. Occasionally, such cells gain a selective growth advantage and are recognized as abnormal clones. These clones may expand to include the entire cell population and show a significantly prolonged lifespan in vitro. The hypothesis is presented that the transforming event occurs in such clones, possibly resulting from a mutational change which occurs at random during cellular proliferation.