Molecular characteristics of neutron-induced thymidine kinase mutants of human B-lymphoblastoid cells

Conventional radiobiologic theory suggests that the LET of a particular type of radiation may influence both the type and the number of lesions which lead to biologically important events such as mutations. Numerous studies have confirmed that the yield of mutants is elevated when high LET radiation is the mutagen, with a maximum yield for particles with an LET (∞) of 100-200 keV/μm. The authors are presently using the technique of Southern blotting to study the DNA structure of thymidine kinase (TK) deficient mutants of the human B-lymphoblastoid cell line TK6 induced by (Pu,Be) neutrons. The active and inactive TK alleles may be distinguished by a restriction fragment length polymorphism revealed upon digestion of DNA with the enzyme SacI and blotting with the human TK cDNA probe. Thus, it is possible to identify major deletions or rearrangements in the induced mutant allele. Preliminary results indicate that 70% (19/27) of neutron-induced mutants with normal growth patterns show major structural alterations in the TK gene