The "recall effect" in radiotherapy: is subeffective, reparable damage involved?

It has been proposed that lethal mutations among the progeny of a surviving cell could be the basis for the recall effect when chemotherapy is applied subsequent to the repair of normal-tissue injury resulting from a course of radiation therapy. Because radiotherapy is usually multifractionated, the possibility exists that repair of heritable injury of this type could occur between fractions as is the case for sublethal damage. To examine this possibility, the endpoint small-colony formation was used--an endpoint which integrates the effects of a number of radiation-induced aberrancies including lethal mutations--and low-dose-rate irradiation. It was found that, even after net surviving fractions comparable to those sought in radiotherapy were reached, little damage remained expressible as a deficiency in the size of the colony generated from a surviving cell. We conclude that the damage expressible as a lethal mutation is reparable and therefore the recall effect must be attributed to some other cellular mechanism.