PMID- 10070969
OWN - NLM
STAT- MEDLINE
DCOM- 19990322
LR  - 20131121
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 59
IP  - 5
DP  - 1999 Mar 1
TI  - Increased ultraviolet sensitivity and chromosomal instability related to P53
      function in the xeroderma pigmentosum variant.
PG  - 1102-8
AB  - The xeroderma pigmentosum (XP) variant (XPV) is a form of XP that has normal
      excision repair but shows defective DNA replication after UV irradiation. In
      developing various transformed fibroblast cell lines from these patients, we have
      found that there are significant phenotypic changes in transformed cells that
      seem to correlate with inactivation of p53. After transformation with SV40, XPV
      cell lines are only slightly UV sensitive, like their primary counterparts, but
      their sensitization with caffeine and the induction of sister chromatid exchanges
      (SCEs) by UV irradiation are greatly enhanced. After transformation by HPV16 E7, 
      which targets the retinoblastoma cell cycle regulatory gene, there is no change
      in the UV sensitivity of XPV cells; but, when transformed by HPV16 E6 or E6 and
      E7 combined, there is a large increase in UV sensitivity and in the induction of 
      SCEs. These changes are not associated with any detectable changes in the
      reactivation of an externally irradiated luciferase expression vector, the
      excision of cyclobutane pyrimidine dimers from bulk DNA, or unscheduled DNA
      synthesis and, therefore, do not involve excision repair. We suggest that if SCEs
      represent homologous recombination between sister chromatids, then in the absence
      of p53 function, the DNA chain arrest typical of UV-damaged XPV cells initiates
      strand exchange during recovery. In untransformed cells with normal p53, the
      preferred mode of recovery would then be replication bypass. The symptoms of
      elevated solar carcinogenesis in XPV patients may, therefore, be associated with 
      increased genomic instability in cells of the skin in which p53 is inactivated by
      UV-induced mutations.
FAU - Cleaver, J E
AU  - Cleaver JE
AD  - Department of Dermatology, University of California at San Francisco, 94143-0750,
      USA. cleaver@itsa.ucsf.edu
FAU - Afzal, V
AU  - Afzal V
FAU - Feeney, L
AU  - Feeney L
FAU - McDowell, M
AU  - McDowell M
FAU - Sadinski, W
AU  - Sadinski W
FAU - Volpe, J P
AU  - Volpe JP
FAU - Busch, D B
AU  - Busch DB
FAU - Coleman, D M
AU  - Coleman DM
FAU - Ziffer, D W
AU  - Ziffer DW
FAU - Yu, Y
AU  - Yu Y
FAU - Nagasawa, H
AU  - Nagasawa H
FAU - Little, J B
AU  - Little JB
LA  - eng
GR  - 1-RO1-ES-8061/ES/NIEHS NIH HHS/United States
GR  - 5-T32-ES07106/ES/NIEHS NIH HHS/United States
GR  - CA47452/CA/NCI NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 3G6A5W338E (Caffeine)
SB  - IM
MH  - Caffeine/pharmacology
MH  - Cell Division/drug effects/radiation effects
MH  - Cell Line
MH  - Cell Line, Transformed
MH  - Cell Survival/drug effects/*radiation effects
MH  - Cell Transformation, Viral
MH  - DNA Repair/radiation effects
MH  - DNA Replication/radiation effects
MH  - Dose-Response Relationship, Radiation
MH  - Fibroblasts
MH  - Genes, Reporter
MH  - *Genes, p53
MH  - *Genetic Variation
MH  - Humans
MH  - Kinetics
MH  - Papillomaviridae/genetics
MH  - Recombinant Proteins/biosynthesis
MH  - Simian virus 40/genetics
MH  - Transfection
MH  - Tumor Suppressor Protein p53/*metabolism
MH  - *Ultraviolet Rays
MH  - Xeroderma Pigmentosum/*genetics
EDAT- 1999/03/10 00:00
MHDA- 1999/03/10 00:01
CRDT- 1999/03/10 00:00
PHST- 1999/03/10 00:00 [pubmed]
PHST- 1999/03/10 00:01 [medline]
PHST- 1999/03/10 00:00 [entrez]
PST - ppublish
SO  - Cancer Res. 1999 Mar 1;59(5):1102-8.