Experimental Study On The Relationship Between Fragile Histidine Triad Gene And Radiation Carcinogenesis

The mechanism which ionization radiation induced tumor isn't clear. To elucidate the mechanism of radiation carcinogenesis will help us to understand the tumors further, provide the scientific evidence for the prevention and treatment of tumors. The fragile histidine triad gene, a putative tumor suppressor gene was found recently. Homozygous deletion of FHIT gene associated with carcinogenesis and development of many kinds of tumors, particularly in tumors resulting from exposure to environmental carcinogens. It was thought to be a target of these carcinogens. And radiation is an environmental carcinogen. The reports about the role of FHIT gene in radiation carcinogenesis aren't found. At first, we establish the leukemia model induced by -ray irradiation in mice. With the methods of Reverse transcription-PCR and cDNA sequencing, the expression of FHIT gene was detected in radiation carcinogenesis. The results show that: 1, The FHIT gene's sequence in normal BALB/c mice compare with the sequence of mice in GeneBank which absents exon 3, but the function of FHIT protien doesn't alter. 2. Abnormal transcripts of FHIT gene were not observed in blood , thymus and marrow of control group. Aberrant transcripts of FHIT gene were detected in blood, thymus and marrow of different dose groups, and the deletion of FHIT gene was confirmed by DNA sequencing. Those deletions were associated with the dose of radiation. 3. The leukemia model in mice were successfully established, and the incidence rate of leukemia is about 33.9% in mice; Abnormal transcripts of FHIT gene were not observed in the control's thymus and blood. In thymus, 9 cases (50% in 18 cases of canceration group) and 4 cases (50% in 8 cases of uncanceration group) exhibited abnormal transcripts of FHIT gene; In blood, 6cases (60% in 10 cases of canceration group) and 6 cases (54.5% in 11 cases of uncanceration group) exhibited abnormal transcripts of FHIT gene, and the deletion of FHIT gene was confirmed by DNA sequencing.These results suggested that: 1 , FHIT gene has a consangnineous correlation with radiation carcinogenesis; 2 , FHIT gene may play an important role in the primary of radiation carcinogenesis; 3 , FHIT gene may play an important role in the development of leukemia induced by y-ray in mice. But further research was expected for the role of FHIT gene in radiation carcinogenesis.