Neutron carcinogenesis. Past, present, and future

An interest in the possible cancer causing ability of neutrons began soon after their discovery. Early use of neutrons from radioactive sources and from cyclotrons led to a need to define risk for such exposures. This need was soon followed by a more tangible need to define risk to the general population of high LET radiation from nuclear fall out and use of the Atomic bomb and possible use of the H-bomb. Neutrons were soon found to be very effective cell killing agents compared to conventional ionizing radiation. However High LET radiation sources and neutrons in particular, come in many different energies and from many types of sources. I will survey the differences between different energy neutrons and conventional types of radiation, particularly with respect to the dose rate of exposures and the influence of repair or lack thereof and more recently the effect of cell cycle distribution on the carcinogenic outcome. I will illustrate these ideas with examples of carcinogenicity studies and mutation studies from my own laboratory and in some cases from the work of others. Lastly I will introduce some possible avenues for molecular studies of neutron effects that might answer such vexing questions as the real risk at very low doses, is repair error free or error prone, do neutrons cause genetic instability for many cell generations after exposure, and others? There remain many questions about the biology of neutron action that require answers if we are to protect the ever increasing number of people exposed to them because of their growing use in medicine, in the military and in commercial industry. (author)