p53 mutations in tumors derived from irradiated human thyroid epithelial cells.
A non-tumorigenic human thyroid epithelial cell line (HTori-3) has been transformed into tumorigenic cells by exposure in vitro to alpha particles or gamma-radiation. These transformants were tumorigenic in athymic nude mice and tumors were transplantable into other nude mice. To further characterize processes involved in neoplastic progression, the tumor cell lines derived from these radiation-induced primary tumors were screened for mutations in the p53 tumor suppressor gene. p53 mutation was detected by single-strand conformation polymorphism (SSCP) analysis of exons 5 to 8 inclusive. Mutations detected by SSCP analysis were confirmed by sequencing. Mutations were detected in all four exons analysed, although there was no correlation between dose, LET or mutation position or frequency. Mutations in p53 exons 6 and 7 have been reported in the childhood papillary thyroid carcinomas in Belarus presumably as a result of radioiodine fall-out. Similarly here, p53 mutations are induced experimentally during the development of human thyroid tumors generated by irradiation of a human thyroid epithelial cell line in vitro.
Gamble
S C
SC
Department of Biology and Biochemistry, Brunel University, Uxbridge, Middlesex, UB8 3PH, UK. simon.gamble@brunel.ac.uk
Cook
M C
MC
Riches
A C
AC
Herceg
Z
Z
Bryant
P E
PE
Arrand
J E
JE
D000512:Alpha Particles; D000818:Animals; D002478:Cells, Cultured / Q000528:radiation effects / Q000637:transplantation; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics*; D004307:Dose-Response Relationship, Radiation; D004847:Epithelial Cells / Q000528:radiation effects / Q000637:transplantation; D005091:Exons / Q000235:genetics / Q000528:radiation effects; D005720:Gamma Rays; D016158:Genes, p53 / Q000528:radiation effects; D006801:Humans; D018499:Linear Energy Transfer; D008168:Lung / Q000166:cytology / Q000528:radiation effects; D051379:Mice; D008819:Mice, Nude; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*; D009928:Organ Specificity; D018807:Polymorphism, Single-Stranded Conformational; D013961:Thyroid Gland / Q000166:cytology* / Q000528:radiation effects; D013964:Thyroid Neoplasms / Q000235:genetics*
D004273:DNA, Neoplasm