Molecular biology in radiation therapy: the potential impact of recombinant technology on clinical practice.
There is good evidence to believe that the most important lesion induced in deoxyribonucleic acid (DNA) by ionizing radiation is a double strand break. Two double strand breaks may interact and rejoin in three different ways. (a) To form a dicentric, which is a lethal event, and will lead to the death of the cell. (b) To form a symmetrical translocation, which may activate an oncogene, and result in, for example, a leukemia or lymphoma. (c) To result in a deletion, which may remove or inactivate a suppressor gene and result in, for example, a solid tumor. Genes identified in mammalian cells may be conveniently grouped into four families. Genes involved in the repair of radiation damage can greatly influence radiosensitivity. Molecular checkpoint genes hold damaged cells in G2 to check for the integrity of their chromosomes before allowing them to proceed into mitosis; consequently, an inactivated checkpoint gene can also result in increased radiosensitivity. Activated oncogenes are associated with only a small proportion of human cancers, and tend to be found more commonly in leukemias and lymphomas and less frequently with solid tumors. A reciprocal translocation is the most likely mechanism by which radiation may activate an oncogene. An inactivated or deleted suppressor gene is commonly associated with a wide range of human cancers. It is becoming increasingly evident that many common cancers do not arise randomly in the population, but that subgroups of individuals are particularly susceptible. The challenge of recombinant technology is that in the near future it may well be possible to determine at birth the susceptibilities of a given individual by identifying mutations in key genes. This is the revolution and challenge we face in the treatment of cancer.
Hall
E J
EJ
Center for Radiological Research, College of Physicians and Surgeons of Columbia University, New York, NY 10032.
D000595:Amino Acid Sequence; D000818:Animals; D004247:DNA / Q000528:radiation effects; D004274:DNA, Recombinant; D005720:Gamma Rays; D016153:Genes, Suppressor; D020022:Genetic Predisposition to Disease; D005821:Genetic Techniques; D006801:Humans; D008967:Molecular Biology; D008969:Molecular Sequence Data; D005810:Multigene Family; D009369:Neoplasms / Q000532:radiotherapy*; D009381:Neoplasms, Radiation-Induced; D009857:Oncogenes; D011878:Radiotherapy / Q000639:trends*; D014162:Transfection; D014178:Translocation, Genetic
D004274:DNA, Recombinant; D004247:DNA