The molecular biology of radiation carcinogenesis.
Major new insights into carcinogenesis have come from recent advances in cellular and molecular biology. The concept of oncogenes provides a simple explanation for how agents as diverse as radiation, chemicals or retroviruses can induce tumors that are indistinguishable one from another. Oncogenes may be activated by a point mutation, by a chromosome translocation, or by amplification. Ionizing radiations are efficient at the first two mechanisms. While oncogenes are frequently associated with leukemias and lymphomas, they are associated with only 10 to 15% of human solid cancers. The importance of the loss of suppressor genes was suggested first from studies with human-hamster hybrid cells, but has since been shown to be of importance in an increasing number of human solid tumors, from rare tumors such as retinoblastoma to more common tumors such as small cell lung cancer and colorectal cancer. The mechanism of somatic homozygosity clearly involves several steps, some of which, such as a deletion, could be readily produced by ionizing radiation. The multi-step nature of carcinogenesis can be demonstrated in the petri dish, where the transfection of multiple oncogenes is required to transform normal cells from short-term explants. It can be shown, too, in colorectal cancer in the human, where the activation of an oncogene and the loss of more than one suppressor gene may be involved in the progression from normal epithelium to a frank malignancy.
Hall
E J
EJ
Center for Radiological Research, College of Physicians and Surgeons of Columbia University, New York.
Freyer
G A
GA
D000818:Animals; D002869:Chromosome Aberrations; D006801:Humans; D008957:Models, Genetic; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*; D009857:Oncogenes; D012190:Retroviridae / Q000235:genetics; D014178:Translocation, Genetic