Health and Biomedical Innovation, Clinical and Health Sciences, University of South Australia, 5000 Adelaide, Australia.
Genome Health Foundation, 5048 North Brighton, Australia.
Mutagenesis. 2023 Dec 19;38(6):305-314. doi: 10.1093/mutage/gead029.
High intake of red meat and/or dairy products may increase the concentration of iron and calcium in plasma-a risk factor for prostate cancer (PC). Despite our understandings of nutrients and their effects on the genome, studies on the effects of iron and calcium on radiation sensitivity of PC patients are lacking. Therefore, we tested the hypothesis that high plasma levels of iron and calcium could increase baseline or radiation-induced DNA damage in PC patients relative to healthy controls. The present study was performed on 106 PC patients and 132 age-matched healthy individuals. CBMN assay was performed to measure mi-cronuclei (MN), nucleoplasmic bridges (NPBs), and nuclear buds (NBuds) in lymphocytes. Plasma concentrations of iron and calcium were measured using inductively coupled plasma atomic emission spectroscopy. MN, NPBs, and NBuds induced by radiation ex vivo were significantly higher in PC patients with high plasma iron (P = .004, P = .047, and P = .0003, respectively) compared to healthy controls. Radiation-induced MN and NBuds frequency were also significantly higher in PC patients (P = .001 and P = .0001, respectively) with high plasma calcium levels relative to controls. Furthermore, radiation-induced frequency of NBuds was significantly higher in PC patients (P < .0001) with high plasma levels of both iron and calcium relative to controls. Our results support the hypothesis that high iron and calcium levels in plasma increases the sensitivity to radiation-induced DNA damage and point to the need of developing nutrition-based strategies to minimize DNA damage in normal tissue of PC patients undergoing radiotherapy.
高摄入红肉和/或乳制品可能会增加血浆中铁和钙的浓度-这是前列腺癌（PC）的一个风险因素。尽管我们了解了营养素及其对基因组的影响，但缺乏关于铁和钙对 PC 患者辐射敏感性影响的研究。因此，我们检验了这样一个假设，即高血浆铁和钙水平可能会增加 PC 患者相对于健康对照者的基线或辐射诱导的 DNA 损伤。本研究共纳入 106 例 PC 患者和 132 名年龄匹配的健康个体。采用彗星试验（CBMN）检测淋巴细胞微核（MN）、核质桥（NPBs）和核芽（NBuds）。采用电感耦合等离子体原子发射光谱法测量血浆中铁和钙的浓度。结果显示，与健康对照组相比，高血浆铁（P =.004，P =.047 和 P =.0003）的 PC 患者辐射诱导的 MN、NPBs 和 NBuds 明显增加。此外，与健康对照组相比，高血浆钙水平的 PC 患者（P =.001 和 P =.0001）辐射诱导的 MN 和 NBuds 频率也明显更高。此外，与健康对照组相比，高血浆铁和钙水平的 PC 患者（P ＜.0001）的辐射诱导 NBuds 频率明显更高。我们的研究结果支持这样一个假设，即高血浆铁和钙水平会增加对辐射诱导的 DNA 损伤的敏感性，并表明需要制定基于营养的策略，以最大限度地减少接受放疗的 PC 患者正常组织中的 DNA 损伤。
