| Co-Investigator(Kenkyū-buntansha) |
MOCHIZUKI Shigenobu Research institute, Division of Pathology CHIBA CANCER CENTER RESEARCH INSTITUTE, 病理研究部, 主任研究員 (60260246)
MIYAUCHI Motohiro Research institute, Division of Pathology CHIBA CANCER CENTER RESEARCH INSTITUTE, 病理研究部, 主任研究員 (70260247)
福嶋 得忍 千葉県がんセンター, 病理研究部, 主任研究員 (50260245)
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| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1996: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1995: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Research Abstract |
Human DNA harbors many vertically transmissible retroviral suquences. Haman T lymphotropic virus type I (HTLV-I) is a horizontally transmissible retrovirus. HTLV-I has been implicated in abult T cell leukemia (ATL), but its etiological rele remains unknown. Our observatons of a higher HTLV-I seroprevalence in cancer patients than in healthy persons led us to survey human tissues for HTLV-I genes (LTR,gag, and/or tax).DNA from blood and tissue specimens was analyzed by PCR-SSCP,direct sequencing, and in situ hybrodization (ISH). The gene product expression was examined by immunostaining. Chromosomal instability was tested by SCE.The ferquency of positivity for HTLV-I related sequences in tumors of nasopharynx, urogenital, bone and soft part, endocrine, respiratory, hematopoietic, skin, germ cell, neural, and gastrointestinal tissues was 100,92.3,88.0,87.5,83.3,76.5,75.0,71.4,44.4, and 33.3%, respectively. These sequences had variable mutations but no homology to HRES-1 sequences. Signal
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s were detected in tumor cells and lymphocytes. DNA from non-tumorous areas also showed signals but with too low amplification to analyze further. DNA from seronegative members of ATL patients'family showed signal patterns distinct from those seen in DNA of patients. Moreover, HTLV-I gene polymorphisms detected in same individuals at different times showed variability. Lymphocyes carrying prototype LTR,gag, and tax sequences showed SCE significantly higher than that of lymphocytes without these sequences when examined following MNNG treatment.The abnormal gene product expressio was observed in nasopharyngeal carcinomas in which genes of both HTLV-I and Epstein-Barr virus were detectable. These findings suggest that HTLV-I related sequences are present in human DNA and cause instability of host cell DNA when they evolve to prototype sequences through rearrangements leading to deregulation of cellulare genes of the host cell upen exposure to carcinogens including viruses. (Supported in part by Grant-in-Aid for Scientific Research (C) , The Ministry f Education, Science, Sports and Culture of Japan.) Less
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