Radiation carcinogenesis and delayed lethal damage in a human thyroid epithelial cell line

Radiation carcinogenesis;DNA damage;Epithelial cells

Mercer, John ; Riches, Andrew Clive ; Riches, Andrew Clive

University:University of St Andrews

Department:Medicine (School of)

关键词: Radiation carcinogenesis;    DNA damage;    Epithelial cells;   

Others  :  https://research-repository.st-andrews.ac.uk/bitstream/handle/10023/9613/JohnMercerPhDThesis.pdf?sequence=2&isAllowed=y

来源: DR-NTU

【 摘 要 】

The human thyroid epithelial cell HTori-3 has been transformed with doses of eitherchronic and acute x-rays or strontium beta particles. Models of the past have reliedupon animal cell systems to mimic in vitro carcinogenesis. The HTori-3 systemhoped to overcome the limitations associated with these types of models by using ahuman thyroid cell line immortalised with the SV40 virus.HTori-3 human thyroid epithelial cells were irradiated in vitro, passaged and thentransplanted into nude mice. Tumours that grew over a 2-6 month period wereexcised and re-established in culture. Samples were stored and all tumours weretaken for histological examination. Chromosome spreads confirmed the humannature of all tumours.Following exposure to acute x-rays in the range of 0.25-2.0 Gy 13 tumours wereobserved in 25 recipients. Following 0.25-2.0 Gy of chronic x-rays 10 tumours from25 recipients were observed. From a single 2 Gy exposure of strontium betaparticles 3 primary tumours from 5 recipients were observed. The largest of thesewas re-transplanted in nude mice resulting in 100% incidence. All tumours wereclassified as undifferentiated anaplastic carcinomas. A small number of tumourswere observed in the control cell lines, these may be the result of a generalinstability found with the partial transformed parental cell line.All 2Gy tumours and those previously established from this laboratory after alpha orgamma radiation were used to test for the presence of the delayed lethal deathphenotype. A number of cell and molecular endpoints were used. These includedplating efficiency, cell adherence, micronucleus formation and p53 status. In allincidences, the reproductive viability of irradiated cells was below that of non-irradiated cells at up to 4 weeks post-irradiation.The HTori-3 cell line and the techniques used to study the delayed effects ofradiation may be applicable to other cell systems and may be a useful model to studythe long-term effects of radiation induced genomic instability.