The emergence of 6-thioguanine-resistant lymphocytes in pediatric cancer patients

Abstract

This paper describes a prospective study and a simultaneous longitudinal study of the frequency of 6-thioguanine- (6TG-) resistant peripheral blood lymphocytes in children with cancer and in controls. Thioguanine resistance was measured autoradiographically by the ability of phytohemagglutinin-stimulated lymphocytes to incorporate tritiated thymidine in the presence or absence of 2 x 10(-4) or 2 x 10(-5) M 6TG. 5 of 29 untreated cancer patients had higher frequencies of 6TG-resistant lymphocytes than any of 116 controls. Patients receiving chemotherapy or radiation therapy showed significantly higher numbers of 6TG-resistant lymphocytes than controls, and in rare patients abnormally high frequencies of 6TG-resistant cells persisted after therapy was discontinued. Among 22 patients studied prospectively before and during therapy, the frequency of 6TG-resistant lymphocytes was significantly higher during therapy. From these results we conclude (1) that some cancer patients have abnormally high frequencies of 6TG-resistant lymphocytes, and (2) cancer therapy either causes selection of 6TG-resistant cells or causes a phenotypic or genotypic change leading to further increases in frequencies of 6TG resistance.