Biologic indicators of exposure: are markers associated with oncogenesis useful as biologic markers of effect?

Radiation-induced molecular and cellular alterations play an important role in the transformation of a normal cell into a cancer cell. However, the basic molecular and cellular alterations upon exposure to ionizing irradiation are still poorly understood. Identification of such alterations would be of importance for the assessment of exposure dose, as well as for the assessment of an exposed individual's risk of developing cancer. Extensive studies of the mechanisms of oncogenesis have led to the identification of altered genes, such as proto-oncogenes and tumor suppressor genes as well as other genes intimately involved in cellular proliferation and differentiation, that are more or less frequently associated with a variety of human malignancies. It can be assumed that at least some of these mechanisms are associated with radiation-induced oncogenesis. The longevity of stem cells, particularly those of the hemopoietic system, makes them the prime target cell population to accumulate genetic alterations due to exposure to a variety of agents. Improvements in purification strategies for hemopoietic stem cells, as well as the availability of sensitive techniques such as the polymerase chain reaction (PCR) and flow cytometry analysis, should allow in-depth studies at the molecular and cellular level after exposure to physical and chemical agents.