UNUSUAL LONG TARGET DUPLICATION BY INSERTION OF INTRACISTERNAL A-PARTICLE ELEMENT IN RADIATION-INDUCED ACUTE MYELOID-LEUKEMIA CELLS IN MOUSE

Retrotransmission into the IL3/GM-CSF gene locus by the retrotransposon intracisternal A-particle (ZAP) had been observed in distinct tumor cell lines. We analyzed the locus in genomes from 7 different myeloid leukemia cell strains which were originally generated by whole-body X-irradiation of the inbred C3H/He mice at a dose of 3 Gy and maintained by in vivo passage. In one leukemia cell strain out of 7 such cases, RFLP of an allele of the interleukin-3 gene was found. Sequence analysis after cloning from the genomic library showed that a type I Delta 2 ZAP element was inserted in the region upstream of the IL-3 gene in the head-to-head orientation. This suggests that the locus in myeloid cells is sensitive for integration of ZAP elements. Additionally, an unusual long target duplication of 82 bp, 14-fold larger than normal one, was found at the junction of the element. This suggests the possibility of a radiation-induced integration mechanism which is distinct from normal retrotransmission.