Do Radiation-Induced Bystander Effects Correlate to the Intrinsic Radiosensitivity of Individuals and Have Clinical Significance?

Abstract

It is well known that patients can vary in their normal tissue response to radiotherapy, and this can be problematic. As a result, radiobiologists have been using in vitro models to assess variation in response and elucidate the genetic determinants of this variation. However, the clinical relevance of these models is currently unknown. In this study, blood samples from healthy controls (n = 20) and colorectal carcinoma patients (n = 60) were cultured in vitro to assess two radiobiological end points in parallel: intrinsic radiosensitivity assayed by chromosomal aberrations (G(2) scores) and radiation-induced bystander effects assayed by viability testing. Increased intrinsic radiosensitivity was observed in colorectal carcinoma donors (55%) compared to the healthy donors (5%) (P < 0.005). Similarly, more pronounced radiation-induced bystander effects were observed in the colorectal carcinoma donors compared to the healthy donors after 24 h exposure but not after 96 h exposure to donor irradiated cell conditioned medium (ICCM) (P < 0.05). All scores were tested for correlation with the age, sex and clinical stage of the colorectal carcinoma patients. The only statistically significant correlation was found in samples from severe Dukes D patients (P < 0.005), which had low/radioresistant G(2) scores. No correlation was found between radiation-induced intrinsic sensitivity and bystander effects, which suggests that they may have separate underlying molecular mechanisms, but they both show clinical relevance in individual patient samples.