Oxidant-Induced Restriction Polymorphism Maps to Kinase Region of C-Abl Oncogene

Abstract

Reactive oxygen species generated by activated human phagoctyes can cause a variety of genetic injuries and produce malignant transformation in target cells. We previously reported that DNA extracted from phagocyte-transformed 10T1/2 mouse fibroblasts contained Msp I-dependent restriction fragment length polymorphisms in the c-abl oncogene. The data suggested that the oxidant-induced RFLP resulted from an alteration in the methylation pattern in c-abl. We have now mapped one of these RFLP to a specific ‘CCGG’ tetramer found within the tyrosine kinase region of the gene. The polymorphic ‘CCGG’ site has been localized to the intron between exon 2 and 3a. Restriction analysis indicates that a repetitive sequence exists within this intron and that the RFLP is associated with this repeat.

Key Words:

• Oxidant
• Phagocyte
• methylation c-abl
• tyrosine kinase
• oxygen radical.