DECREASED DNA-REPAIR SYNTHESIS AND DEFECTIVE COLONY-FORMING ABILITY OF ATAXIA TELANGIECTASIA FIBROBLAST CELL STRAINS TREATED WITH N-METHYL-N'-NITRO-N-NITROSOGUANIDINE

Abstract

DNA repair synthesis and post-treatment colony-forming ability were measured in 6 human fibroblast cell strains [CRL 1312, CRL 1343, CRL 1347, AT3BI, AT5BI, AT81CTO] derived from patients with the autosomal recessive disorder, ataxia telangiectasia (AT), and 5 cell strains [CRL 1295, CRL 1220, CRL 1187, CRL 1224, WI 38] from normal individuals. All 11 cell strains showed approximately equal levels of DNA repair synthesis after methyl methanesulfonate and UV light treatments assayed by the benzoylated naphthoylated diethylaminoethyl-cellulose method. Four AT cell strains [CRL 1312, AT3BI, CRL 1343, AT81CTO] exhibited 27-41% of the repair shown by normal cell strains after treatment with N-methyl-N''-nitro-N-nitrosoguanidine (MNNG). Two AT cell strains [AT5BI, CRL 1347] had normal levels of repair synthesis after MNNG treatment. All the AT strains tested had normal survival after treatment with methyl methanesulfonate and UV light as assayed by post-treatment colony-forming ability. The 6 AT cell strains exhibited diminished survival after MNNG treatment. The inhibition of [3H]thymidine uptake as a function of MNNG concentration was similar for all the normal and AT cell strains tested. [These data are discussed with regard to proper therapy regimens in AT patients with tumors].