Jones, N. K. | bioRxiv Science

bioRxiv2025

Far-Ultraviolet Light Causes Direct DNA Damage in Human Lung Cells and Tissues

Far-ultraviolet C (Far-UVC) radiation, with a wavelength range from 200 to 235 nm, is germicidal and holds potential for clinical applications. However, its use against deep-seated and internal infections, such as those affecting the lungs, remains less well established. The safety profile of Far-UVC irradiation requires further investigation across different human tissues. In this study, we utilised a krypton-chloride (KrCl) excimer lamp and a pulsed laser system to examine the effects of Far-UVC irradiation on human lung cells in vitro and primary human tracheal tissue. Primary human tracheal tissue and cells exposed to continuous wave (222 nm) and pulsed 206 nm and 222 nm light at doses of 5, 25, and 50 mJ/cm2 exhibited Deoxyribonucleic acid (DNA) damage, including phosphorylation of {gamma}H2AX (Ser139). The continuous wave and pulsed 222 nm irradiation caused the formation of pyrimidine-pyrimidone (6-4) photoproducts. Irradiated human lung cells demonstrated reduced viability in vitro, and increased lactate dehydrogenase release into the culture medium 48 hours post-irradiation. Our findings reveal that even low doses of Far-UVC (206 nm, 222 nm) light can penetrate monolayers of human lung epithelial cells, causing direct DNA damage in the form of (6-4) photoproducts and DNA double-strand breaks, ultimately leading to cell death.

cell biology↗

bioRxiv2024

Renal arterial dysfunction, impaired pressure natriuresis and salt-sensitivity in a mouse model of Cushing syndrome

BackgroundCushing Syndrome arises from endogenous overproduction of ACTH by a tumour or is acquired through chronic exposure to glucocorticoid medication. Hypertension is a major complication, increasing cardiovascular risk, but underlying mechanisms are not clearly defined. MethodsWe infused male C57BL/6J mice with ACTH or vehicle for 14-21 days, inducing cardinal features of Cushing Syndrome. The renal pressure natriuresis response was measured under anesthesia and ex vivo artery function assessed by myography. ResultsACTH infusion blunted the natriuretic and diuretic responses to incremental increases in blood pressure. Renal hemodynamics did not change with blood pressure in controls, but renal autoregulation was impaired in ACTH mice. The ex vivo contractile response of the renal artery to phenylephrine was diminished in Cushing Syndrome mice, as was endothelium-dependent and endothelium-independent relaxation. On 0.3% sodium diet, there was no evidence of sodium retention in ACTH-treated mice but the diurnal rhythm of sodium excretion was abnormal and mice had non-dipping BP. The Cushing Syndrome model also displayed enhanced salt preference and amplified salt-sensitive blood pressure. ConclusionCushing Syndrome induces a cluster of phenotypes impacting sodium homeostasis and blood pressure regulation. Hypertension, salt-sensitivity and non-dipping blood pressure are important cardiovascular risk factors, and, beyond Cushing Syndrome, our findings are relevant to obesity and the metabolic syndrome, in which tissue glucocorticoid homeostasis is abnormal.

physiology↗