MUTATION-INDUCTION BY UV-LIGHT IN RETROVIRAL HPRT CDNA INTEGRATED AT VARIOUS CHROMOSOMAL POSITIONS IN REPAIR-DEFICIENT HAMSTER-CELLS

Mutation induction by UV irradiation was studied in a retroviral vecto r integrated in one copy per cell at various chromosomal positions. As a mutational target, hamster hprt cDNA was present on the retroviral vector. To minimize the influence of repair we used repair-deficient h amster cells, V-H1 and UV5, as a recipient for the vector. There is no major influence of chromosomal position on UV-induced mutation freque ncy and spectrum because no statistically significant difference betwe en mutation induction in retroviral cDNA copies integrated at differen t chromosomal sites was observed. However, a major difference was foun d in mutation induction between the endogenous hamster hprt gene and t he retroviral cDNA copies. Most noticeable was the absence in the cDNA of the strong strand bias for mutation induction, which was reported for the endogenous hprt gene. Our results with the hprt cDNA exclude a s a general phenomenon a difference in mutation induction for leading and lagging strand DNA replication, which was proposed as an explanati on for this strand bias in the endogenous gene. The similarity of muta tion induction in the different retroviral cDNA copies, all directly s urrounded by the same DNA sequence elements, together with the marked difference between the mutation induction in the endogenous gene and t he cDNA copies may point to an important role of chromatin structure i n mutation induction.