ULTRAVIOLET HYPERMUTABILITY OF A SHUTTLE VECTOR PROPAGATED IN XERODERMA-PIGMENTOSUM VARIANT CELLS

被引:64
作者
WATERS, HL
SEETHARAM, S
SEIDMAN, MM
KRAEMER, KH
机构
[1] NCI,MOLEC CARCINOGENESIS LAB,BLDG 37,ROOM 3E24,BETHESDA,MD 20892
[2] OTSUKA PHARMACEUT CO LTD,ROCKVILLE,MD
关键词
DNA REPAIR; SKIN CANCER; SUPF TRANSFER RNA; LYMPHOBLASTOID CELLS;
D O I
10.1111/1523-1747.ep12371686
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
Patients with the variant form of xeroderma pigmentosum (XP) have clinical Xp including a high frequency of skin cancer but, in contrast to the other forms of XP, have normal post-ultraviolet (UV) DNA excision repair and nearly normal post-UV survival. However, like excision repair-deficient XP cells, the XP variant cells are UV hypermutable. We used a UV-treated plasmid shuttle vector, pZ189, to examine the DNA repair defect in lymphoblastoid cells from an XP variant patient, XPPHBE, and a normal control. Plasmid repair, mutagenesis, and replication occur within transfected cells in a process dependent on the cells' repair capacity. With the XP variant cells post-UV, plasmid survival was normal with but there was an abnormally increased post-UV plasmid mutation frequency. Sequence analysis of the mutated plasmids revealed an increased frequency of plasmids with single base substitution mutations with the XP variant cells. As in earlier studies with UV mutagenesis, there was a predominance of G:C-->A:T base substitution mutations with plasmids recovered from both cell lines. The frequency of G:C-->C:G transversions was significantly higher with plasmids recovered from the XP variant cells than from normal cells. The location of mutations in the marker gene was non-random with different mutagenic hotspots found in plasmids recovered from the XP variant cells and from the normal cells. This study suggests that plasmid UV hypermutability in the presence of normal UV survival may be related to the increased UV skin cancer susceptibility of XP variant patients.
引用
收藏
页码:744 / 748
页数:5
相关论文
共 48 条
[1]   XERODERMA PIGMENTOSUM NEUROLOGICAL ABNORMALITIES CORRELATE WITH COLONY-FORMING ABILITY AFTER ULTRAVIOLET-RADIATION [J].
ANDREWS, AD ;
BARRETT, SF ;
ROBBINS, JH .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1978, 75 (04) :1984-1988
[2]   INFLUENCE OF CAFFEINE ON CELL SURVIVAL IN EXCISION-PROFICIENT AND EXCISION-DEFICIENT XERODERMA PIGMENTOSUM AND NORMAL HUMAN CELL STRAINS FOLLOWING ULTRAVIOLET-LIGHT IRRADIATION [J].
ARLETT, CF ;
HARCOURT, SA ;
BROUGHTON, BC .
MUTATION RESEARCH, 1975, 33 (2-3) :341-346
[3]   CODING PROPERTIES OF POLY(DEOXYCYTIDYLIC ACID) TEMPLATES CONTAINING URACIL OR APYRIMIDINIC SITES - INVITRO MODULATION OF MUTAGENESIS BY DEOXYRIBONUCLEIC-ACID REPAIR ENZYMES [J].
BOITEUX, S ;
LAVAL, J .
BIOCHEMISTRY, 1982, 21 (26) :6746-6751
[4]   THE STUDY OF DNA-REPAIR DEFECTS USING [I-125]IODODEOXYCYTIDINE INCORPORATION AS AN ASSAY FOR THE GROWTH OF HERPES-SIMPLEX VIRUS [J].
BOORSTEIN, R ;
CAMPISI, J ;
PARDEE, AB .
MUTATION RESEARCH, 1983, 112 (02) :85-95
[5]   PHOTOPRODUCT FREQUENCY IS NOT THE MAJOR DETERMINANT OF UV BASE SUBSTITUTION HOT-SPOTS OR COLD SPOTS IN HUMAN-CELLS [J].
BRASH, DE ;
SEETHARAM, S ;
KRAEMER, KH ;
SEIDMAN, MM ;
BREDBERG, A .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (11) :3782-3786
[6]   RESTRICTED ULTRAVIOLET MUTATIONAL SPECTRUM IN A SHUTTLE VECTOR PROPAGATED IN XERODERMA PIGMENTOSUM-CELLS [J].
BREDBERG, A ;
KRAEMER, KH ;
SEIDMAN, MM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1986, 83 (21) :8273-8277
[7]  
BURK PG, 1971, J LAB CLIN MED, V77, P759
[8]   SIMILAR DEFECTS IN DNA-REPAIR AND REPLICATION IN THE PIGMENTED XERODERMOID AND THE XERODERMA PIGMENTOSUM VARIANTS [J].
CLEAVER, JE ;
ARUTYUNYAN, RM ;
SARKISIAN, T ;
KAUFMANN, WK ;
GREENE, AE ;
CORIELL, L .
CARCINOGENESIS, 1980, 1 (08) :647-655
[10]  
Cleaver JE, 1989, METABOLIC BASIS INHE, V6th, P2949