Wang Chung-Ching, Chen Wei-Liang, Hsiung Chia-Ni, Chiang Sheng-Ta, Wang Ying-Chuan, Loh Ching-Hui, Lin I-Shen, Chen Hong-I, Liou Saou-Hsing
Division of Family Medicine, Department of Family and Community Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China.
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Armed Forces General Hospital, National Defense Medical Center, Taichung, Taiwan, Republic of China.
Occup Environ Med. 2017 Jan;74(1):30-38. doi: 10.1136/oemed-2016-103816. Epub 2016 Sep 27.
We investigated the relationship between 4,4'-methylene-bis(2-chloroaniline) (MBOCA) exposure and micronucleus (MN) frequency, and how this association was affected by genetic polymorphism of the cytochrome P450 enzyme (CYP3A4).
We divided the study population into an exposed group (n=44 with total urine MBOCA ≥20 μg/g creatinine) and a control group (n=47 with total urine MBOCA <20 μg/g creatinine). Lymphocyte MN frequency (MNF) and micronucleated cell (MNC) frequency were measured by the cytokinesis-block MN assay method. MNF reported as the number of micronuclei in binucleated cells per 1000 cells, and MNC reported as the number of binucleated cells with the presence of MN per 1000 cells. CYP3A4 alleles were measured by PCR-based restriction fragment length polymorphism (PCR-RFLP).
The mean MNF (6.11 vs 4.46 MN/1000 cells, p<0.001) and MNC (5.75 vs 4.15 MN/1000 cells, p<0.001) in the exposed workers was significantly higher than that in the controls. The CYP3A4 polymorphism A/A+A/G influenced the difference in the mean MNF (5.97 vs 4.38 MN/1000 cells, p<0.001) and MNC (5.60 vs 4.15 MN/1000 cells, p<0.001) between the MBOCA-exposed and control groups. After adjusting risk factors, the MNF level in the MBOCA-exposed workers was 0.520 MN cells/1000 cells (p<0.001) higher than the control group among the CYP3A4 A/A+A/G genotype. Similarly, the MNC level in the MBOCA-exposed workers was 0.593 MN/1000 cells (p<0.001) higher than the control group among the CYP3A4 A/A+A/G genotype. However, the difference in adjusted MNF and MNC between the exposed and control groups was not significant for the CYP3A4 polymorphism with the G/G genotype.
We recommend that lymphocytes MNF and MNC are good indicators to evaluate MBOCA genotoxicity. Individuals with the CYP3A4 polymorphism A/A and A/G genotypes appear to be more susceptible to MBOCA genotoxicity.
我们研究了4,4'-亚甲基双（2-氯苯胺）（MBOCA）暴露与微核（MN）频率之间的关系，以及细胞色素P450酶（CYP3A4）的基因多态性如何影响这种关联。
我们将研究人群分为暴露组（n = 44，尿中总MBOCA≥20μg/g肌酐）和对照组（n = 47，尿中总MBOCA<20μg/g肌酐）。采用胞质分裂阻滞微核试验方法测量淋巴细胞微核频率（MNF）和微核化细胞（MNC）频率。MNF报告为每1000个双核细胞中的微核数量，MNC报告为每1000个存在微核的双核细胞数量。通过基于聚合酶链反应的限制性片段长度多态性（PCR-RFLP）测量CYP3A4等位基因。
暴露工人的平均MNF（6.11对4.46个微核/1000个细胞，p<0.001）和MNC（5.75对4.15个微核/1000个细胞，p<0.001）显著高于对照组。CYP3A4基因多态性A/A + A/G影响了MBOCA暴露组和对照组之间平均MNF（5.97对4.38个微核/1000个细胞，p<0.001）和MNC（5.60对4.15个微核/1000个细胞，p<0.001）的差异。在调整风险因素后，CYP3A4 A/A + A/G基因型中，MBOCA暴露工人的MNF水平比对照组高0.520个微核细胞/1000个细胞（p<0.001）。同样，CYP3A4 A/A + A/G基因型中，MBOCA暴露工人的MNC水平比对照组高0.593个微核/1000个细胞（p<0.001）。然而，对于CYP3A4基因多态性G/G基因型，暴露组和对照组之间调整后的MNF和MNC差异不显著。
我们建议淋巴细胞MNF和MNC是评估MBOCA遗传毒性的良好指标。具有CYP3A4基因多态性A/A和A/G基因型的个体似乎对MBOCA遗传毒性更敏感。
