School of Public Health, Hongqiao International Institute of Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
Shanghai 10th People's Hospital, Shanghai, People's Republic of China.
Environ Mol Mutagen. 2020 Apr;61(4):456-464. doi: 10.1002/em.22348. Epub 2019 Dec 6.
The rodent Pig-a assay has been used extensively as a potential regulatory assay for evaluating the in vivo mutagenicity of test substances. Although the assay can be conducted in different mammalian species, there have been only a few reports describing its use in humans, and rarely in genotoxicant-exposed human populations. In this study, PIG-A mutation frequencies (MFs) were evaluated in 36 azathioprine (AZA; human carcinogen)-treated inflammatory bowel disease (IBD) patients and 36 healthy volunteers. IBD patients exhibited a slight but statistically higher MF (6.10 ± 4.44 × 10 ) than healthy volunteers (4.97 ± 2.74 × 10 ) (P = 0.0489). The estimated relative risk for the exposed patients was 1.22 which indicated that AZA is a risk factor for inducing PIG-A mutation. However, the PIG-A MF showed no associations with AZA treatment duration or total AZA exposure. In addition, we performed the cytokinesis-block micronucleus test on the same samples. The frequencies of micronuclei (MN) and nuclear buds (NBUD) in IBD patients (MN: 4.70 ± 2.86‰; NBUD: 1.89 ± 0.95‰) were significantly higher than in healthy volunteers (MN: 1.47 ± 0.77‰, P < 0.001; NBUD: 0.90 ± 0.58‰, P = 0.004). MN frequency also had significant correlations with AZA treatment duration (P = 0.011) and total AZA exposure (P = 0.018). Our findings indicate that AZA-treated IBD patients have only a marginally significant increase in PIG-A MF; in contrast, a much stronger AZA-associated increase in genotoxicity was detected with the lymphocyte MN assay. Environ. Mol. Mutagen. 2019. © 2019 Wiley Periodicals, Inc.
啮齿动物 Pig-a 检测已被广泛用于评估测试物质体内致突变性的潜在监管检测。尽管该检测可在不同的哺乳动物物种中进行，但仅有少数报道描述了其在人类中的应用，在接触遗传毒物的人群中则更为罕见。在这项研究中，我们评估了 36 名接受巯嘌呤（AZA；人类致癌物）治疗的炎症性肠病（IBD）患者和 36 名健康志愿者的 PIG-A 突变频率（MF）。IBD 患者的 MF（6.10±4.44×10 ）略高于健康志愿者（4.97±2.74×10 ），但具有统计学意义（P=0.0489）。暴露患者的估计相对风险为 1.22，表明 AZA 是诱导 PIG-A 突变的危险因素。然而，PIG-A MF 与 AZA 治疗持续时间或总 AZA 暴露无关。此外，我们对同一批样本进行了细胞有丝分裂阻断微核试验。IBD 患者的微核（MN）和核芽（NBUD）频率（MN：4.70±2.86‰；NBUD：1.89±0.95‰）显著高于健康志愿者（MN：1.47±0.77‰，P<0.001；NBUD：0.90±0.58‰，P=0.004）。MN 频率与 AZA 治疗持续时间（P=0.011）和总 AZA 暴露（P=0.018）也有显著相关性。我们的研究结果表明，接受 AZA 治疗的 IBD 患者的 PIG-A MF 仅略有增加；相比之下，用淋巴细胞 MN 试验检测到的与 AZA 相关的遗传毒性增加更为明显。环境分子突变学。2019. © 2019 Wiley Periodicals, Inc.
