Liu Qianying, Lei Zhixin, Wu Qin, Huang Deyu, Xie Shuyu, Wang Xu, Pan Yuanhu, Yuan Zonghui
National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, China.
Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Huazhong Agricultural University, Wuhan, China.
Front Pharmacol. 2018 Apr 10;9:361. doi: 10.3389/fphar.2018.00361. eCollection 2018.
Mequindox (MEQ), acting as an inhibitor of deoxyribonucleic acid (DNA) synthesis, is a synthetic heterocyclic -oxides. To investigate the potential carcinogenicity of MEQ, four groups of Kun-Ming (KM) mice (50 mice/sex/group) were fed with diets containing MEQ (0, 25, 55, and 110 mg/kg) for one and a half years. The result showed adverse effects on body weights, feed consumption, hematology, serum chemistry, organ weights, relative organ weights, and incidence of tumors during most of the study period. Treatment-related changes in hematology, serum chemistry, relative weights and histopathological examinations revealed that the hematological system, liver, kidneys, and adrenal glands, as well as the developmental and reproductive system, were the main targets after MEQ administration. Additionally, MEQ significantly increased the frequency of micronucleated normochromatic erythrocytes in bone marrow cells of mice. Furthermore, MEQ increased the incidence of tumors, including mammary fibroadenoma, breast cancer, corticosuprarenaloma, haemangiomas, hepatocarcinoma, and pulmonary adenoma. Interestingly, the higher incidence of tumors was noted in M25 mg/kg group, the lowest dietary concentration tested, which was equivalent to approximately 2.25 and 1.72 mg/kg b.w./day in females and males, respectively. It was assumed that the lower toxicity might be a reason for its higher tumor incidence in M25 mg/kg group. This finding suggests a potential relationships among the dose, general toxicity and carcinogenicity , and further study is required to reveal this relationship. In conclusion, the present study demonstrates that MEQ is a genotoxic carcinogen in KM mice.
乙酰甲喹（MEQ）是一种合成的杂环氧化物，可作为脱氧核糖核酸（DNA）合成的抑制剂。为研究MEQ的潜在致癌性，将四组昆明（KM）小鼠（每组雌雄各50只）喂食含MEQ（0、25、55和110毫克/千克）的饲料，持续一年半。结果显示，在研究的大部分时间段内，MEQ对体重、采食量、血液学指标、血清生化指标、器官重量、相对器官重量和肿瘤发生率均有不良影响。血液学、血清生化、相对重量和组织病理学检查中与处理相关的变化表明，血液系统、肝脏、肾脏、肾上腺以及发育和生殖系统是给予MEQ后的主要靶器官。此外，MEQ显著增加了小鼠骨髓细胞中微核正染红细胞的频率。而且，MEQ增加了肿瘤的发生率，包括乳腺纤维腺瘤、乳腺癌、肾上腺皮质瘤、血管瘤、肝癌和肺腺瘤。有趣的是，在测试的最低膳食浓度M25毫克/千克组中观察到较高的肿瘤发生率，该浓度在雌性和雄性小鼠中分别相当于约2.25毫克/千克体重/天和1.72毫克/千克体重/天。据推测，较低的毒性可能是其在M25毫克/千克组中肿瘤发生率较高的原因。这一发现提示了剂量、一般毒性和致癌性之间的潜在关系，需要进一步研究以揭示这种关系。总之，本研究表明MEQ在KM小鼠中是一种遗传毒性致癌物。
