Xeroderma pigmentosum variant cells are resistant to immortalization
- Univ. of California, San Francisco, CA (United States)
We have attempted to immortalize fibroblasts from several Xeroderma pigmentosum variant (XPV) patients to better characterize this disease. These patients exhibit sun sensitivity and highly elevated skin cancer rates. It is believed that the defect in these cells involves post replication repair of DNA damage, but the molecular mechanisms and their involvement in patient`s phenotypes remain unknown. Human cells undergo senescence and stop growing after a period of growth in culture, making prolonged studies difficult or impossible. For this reason, immortal cell lines are essential. We have attempted to immortalize XPV cells by: spontaneous transformation, transfection with pSV40 ori (a plasmid containing the SV40 large T-antigen), transfection with pSV40 ori and exposure to 300 rads of x-rays, transfection with pSV40 ori, exposure to 200 rads of x-rays, and treatment with 0.5mM ethyl methanesulfonate, and infection with SV40 virus (strain 776). Despite the fact that some experiments had as many as 2x10{sup 8} cells, we were unable to immortalize any of the cells from our patients. We also obtained several XPV lines from other laboratories which had been transformed with pSV40 ori, but none of them proved to be immortalized either. We suspect that the presumed mutation in XPV cells is in some way interfering with SV40 large T-antigen induced immortalization.
- Research Organization:
- OAK (Oakland Operations Office, Oakland, CA)
- Sponsoring Organization:
- USDOE
- DOE Contract Number:
- AC03-76SF01012
- OSTI ID:
- 88928
- Report Number(s):
- CONF-9405324-; ISSN 0893-6692; TRN: 95:004220-0074
- Journal Information:
- Environmental and Molecular Mutagenesis, Vol. 23, Issue Suppl.23; Conference: 25. annual meeting of the Environmental Mutagen Society, Portland, OR (United States), 7-12 May 1994; Other Information: PBD: 1994
- Country of Publication:
- United States
- Language:
- English
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