Characterisation of a bystander effect induced in human tissue explant cultures by low let radiation.
The existence of a bystander effect following both alpha and gamma irradiation of many cell lines is not now in dispute. The significance of this effect for cancer risk assessment and radiotherapy treatment planning requires demonstration of its relevance in vivo. The problem in demonstrating the existence of the effect in vivo is that other systemic effects may mask or confound the effect being investigated and it is practically impossible to attribute an effect in a particular cell to a signal produced in another irradiated cell. To approach this problem, an assay has been developed where fragments of human tissue can be irradiated ex vivo and the media harvested and added to unirradiated, clonogenic cells which have a well characterised and stable response to the bystander signal. The variation in the production of a signal from patient to patient can thus be assessed. The results of a study using tissue from over 100 patients attending Beaumont and St Vincent's Hospitals in Dublin for investigation of urological disorders including follow-up after treatment for transitional cell carcinoma (TCC) and resection of suspect prostatic lesions, are now available. Blood samples from the prostate group were also obtained. The results show that there is variation in the effect of the signal produced by irradiated tissue from different patients. This holds for bladder, prostate and blood. Gender, smoking status and the existence of a malignancy influence the expression of the signal by normal tissue. Male gender, smoking and a pre-existing malignancy all reduce the amount or effect of the signal produced into medium when the tissue is exposed. The effects of exposure to medium containing the signal are transmitted to distant progeny of the exposed cell population. The results may be important not only for understanding radiation risk mechanisms for protection but also for radiotherapy treatment planning where they may open new avenues for development of drugs for combined therapy.
Mothersill
C
C
Radiation and Environmental Science Centre, Dublin Institute of Technology, Kevin Street, Dublin 8, Ireland. cmothersill@rsc.iol.ie
O'Malley
K
K
Seymour
C B
CB
D000512:Alpha Particles; D001706:Biopsy; D024201:Bystander Effect / Q000528:radiation effects*; D002470:Cell Survival / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000528:radiation effects; D018499:Linear Energy Transfer; D008297:Male; D009924:Organ Culture Techniques; D011467:Prostate / Q000166:cytology / Q000528:radiation effects; D001743:Urinary Bladder / Q000166:cytology / Q000528:radiation effects