Ponnaiya, B. | bioRxiv Science

bioRxiv2022

No evidence of induced skin cancer or other skin abnormalities after long term (66 week) chronic exposure to 222-nm far-UVC radiatio

Far-UVC radiation, typically defined as 200-235 nm, has similar or greater anti-microbial efficacy compared to conventional 254-nm germicidal radiation. In addition, biophysical considerations of the interaction of far-UVC with tissue, as well as multiple short-term safety studies in animal models and humans, suggest that far-UVC exposure may be safe for skin and eye tissue. Nevertheless, the potential for skin cancer after chronic long-term exposure to far-UVC has not been studied. Here, we assessed far-UVC induced carcinogenic skin changes and other pathological dermal abnormalities in 96 SKH-1 hairless mice of both sexes that were exposed to average daily dorsal skin doses of 396 mJ/cm2, 126 mJ/cm2 or 56 mJ/cm2 of 222 nm far-UVC radiation for 66 weeks, 5 days per week, 8 hours per day, as well as similarly-treated unexposed controls. No evidence for increased skin cancer, abnormal skin growths, or incidental skin pathology findings was observed in the far-UVC exposed mice. In addition, there were no significant changes in morbidity or mortality. The findings from this study support the long-term safety of long-term chronic exposure to far-UVC radiation, and therefore its potential suitability as a practical anti-microbial approach to reduce airborne viral and bacterial loads in occupied indoor settings.

cancer biology↗

bioRxiv2022

LET-dependence of radiation-induced makers of Immunogenic Cell Death in human cancer cell lines

PurposeIt has been suggested that heavy-ion radiation therapy may contribute to the control of distal metastases. These distant responses may include immune cell activation. Immunostimulation resulting from radiation-induced immunogenic cell death (ICD) of cancer cells, leads to the recruitment of anti-tumor T cells. Specific markers of ICD include translocation of calreticulin (CRT) and extracellular release of high mobility group box 1 protein (HMGB1), and ATP. However, the LET dependence of these effects remains unknown. Materials and MethodsExpression of the molecular indicators described above were tested in a panel of human cancer cell lines, that included pancreatic cancer (Panc1 and Paca2), glioblastoma (U87 and LN18) and melanoma (HTB129 and SK-Mel5). Cells were irradiated with 5 Gy of particles spanning a range of LETs, from 10 KeV/m to 150 KeV/m and assayed for relocalization of calreticulin and release of HMGB1 and ATP were assayed 24 hours later. ResultsIn the pancreatic cancer cell lines (Panc1 and Paca2) there was a continued increase in the membrane relocalization of calreticulin as a function of increasing LET up to 150 KeV/m. The melanoma cell lines, HTB129 and Sk-Mel5 showed similar patterns. In contrast, calreticulin levels were higher, but not LET-dependent, in irradiated U87 and LN18 (glioblastoma) lines. With the exception of the response in Paca2, increases in LET correlated with increases in HMGB1 that seemed to peak at 100 KeV/m and then either remain unchanged or decrease at 150 KeV/m. while the ATP levels were elevated in media from some of the irradiated groups, there were no clear patterns either by cell type or LET. ConclusionsOur results indicate that at equal doses, although there is an overall trend of increases in the responses to increasing LETs, there are significant cell line-specific differences in the patterns of expression of these key ICD markers.

cell biology↗