CORRELATION OF (6-4)PHOTOPRODUCT FORMATION WITH TRANSFORMING MUTATIONS IN UV-IRRADIATED HA-RAS

被引:5
作者
YAGI, T [1 ]
MORIMOTO, T [1 ]
TAKEBE, H [1 ]
机构
[1] KYOTO UNIV,GRAD SCH MED,DEPT RADIAT GENET,SAKYO KU,KYOTO 60601,JAPAN
关键词
D O I
10.1093/carcin/16.4.689
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Sites and types of mutations in relation to the amount of cyclobutane pyrimidine dimers (CPDs) and (6-4)photoproducts in UV-irradiated normal Ha-ms sequences were investigated, Mouse BALB/C 3T3 cells were transfected with W-irradiated pYN-mHras plasmids containing mouse normal Ha-ras sequences, and transformed foci developed, Direct DNA sequencing of the Ha-ras retrieved from the foci revealed that most mutations (23/24, 96%) took place at dipyrimidine sequences, and the C-->T transition at the 3'-cytosine in 5'-TC or 5'-CC sequences was predominant (17/24, 71%) in codons 12, 13 and 60, In codon 61, where 5'-TC or 5'-CC is absent, two mutations were found at: the 5'-TT sequence. More (6-4)photoproducts were produced than CPDs in codons 12, 13 and 60, and more CPDs were produced than (6-4)photoproducts in codon 61. These results suggest that (6-4)photoproducts are the major lesion leading to the mutations in the mouse Ha-ras sequence and subsequent transformation of BALB/C 3T3 cells.
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页码:689 / 695
页数:7
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共 34 条
[1]  
Wood R.D., Skopek T.R., Hutchinson S., Changes in DNA base sequence induced by targeted mutagenesis of Lambda phage by ultraviolet light, J. Mol Biol, 173, pp. 273-291, (1984)
[2]  
Bredberg A., Kraemer K.H., Seidman J.M., Restricted ultraviolet mutational spectrum in a shuttle vector propagated in xeroderma pigmentosum cells, Proc. Natl Sci. Acad. USA, 83, pp. 8273-8277, (1986)
[3]  
Drobetsky E.A., Grosovsky J., Glickman B.W., The specificity of UV-induced mutations at an endogenous locus in mammalian cells, Proc. Natl Sci. Acad. USA, 84, pp. 9103-9107, (1987)
[4]  
Yagi T., Tatsumi-Miyajima J., Sato M., Kraemer K.H., Takebe H., Analysis of point mutations in an ultraviolet-irradiated shuttle vector plasmid propagated in cells from Japanese xeroderma pigmentosum patients in complementation groups A and F, Cancer Res, 51, pp. 3177-3182, (1991)
[5]  
Urbach F., Photocarcinogenesis: Past, present and future, Frontiers of Photobiology, pp. 403-413, (1993)
[6]  
Barbacid M., Ras genes, Ann. Rev. Biochem, 56, pp. 779-827, (1987)
[7]  
Balmain A., Brown K., Oncogene activation in chemical carcinogenesis, Adv. Cancer Res, 51, pp. 147-182, (1988)
[8]  
Ananthaswamy H.N., Price J.E., Goldberg L.H., Bales E.S., Detection and identification of activated oncogenes in human skin cancels occurring on sun-exposed body sites, Cancer Res, 48, pp. 3341-3346, (1988)
[9]  
Vander Schroeffd G., Evers L.M., Boot A.J.M., Bos J.L., Ras oncogene mutations in basal cell carcinomas and squamous cell carcinomas of human skin, J. Invest Dermatol, 94, pp. 423-425, (1990)
[10]  
Pierceall W.E., Knpke M.L., Ananthaswamy H.N., N-ras mutation in ultraviolet radiation-induced murine skin cancers, Cancer Res, 52, pp. 3946-3951, (1992)