N.N. Petrov National Medical Research Center of Oncology, Saint Petersburg, Russia; Nobel LTD, Saint-Petersburg, Russia.
Petersburg Nuclear Physics Institute Named By B.P. Konstantinov of NRC "Kurchatov Institute", Gatchina, Russia.
Environ Res. 2021 Jan;192:110321. doi: 10.1016/j.envres.2020.110321. Epub 2020 Oct 17.
The genotoxic and antigenotoxic potential of BP-C2, a novel lignin-derived polyphenolic composition with ammonium molybdate, was investigated as a radioprotector/radiomitigator for civil applications and as a medical countermeasure for radiation emergencies. Using the alkaline comet assay and methyl methanesulfonate (MMS, 40 mg/kg) as the DNA-damaging agent, these effects of BP-C2 on liver, bone marrow cells and blood leukocytes in rats were studied. The DNA damage was estimated by the DNA content in the comet tail (TDNA, %) 1, 6 and 18 h post exposure to MMS. BP-C2 at doses of 20, 200 and 2000 mg/kg did not exert genotoxic activity in the tested tissues in rats. BP-C2 administered at doses of 20, 100 and 200 mg/kg 1 h before MMS significantly (p < 0.01) mitigated MMS-induced DNA damage, showing a strong genoprotective effect in the liver. In blood leukocytes and bone marrow samples of animals treated with BP-C2, the TDNA % was slightly higher than in the negative control (vehicle) but significantly lower than in the positive control (MMS). Thus, BP-C2 exerted a genoprotective effect against MMS-induced DNA damage to a greater extent towards liver cells, requiring further evaluation of this substance as a genoprotective agent.
BP-C2 是一种新型木质素衍生的多酚化合物,含有钼酸铵,具有遗传毒性和抗原毒性潜力。作为民用辐射防护剂/缓解剂和辐射紧急情况的医疗对策进行研究。采用碱性彗星试验和甲磺酸甲酯(MMS,40mg/kg)作为 DNA 损伤剂,研究 BP-C2 对大鼠肝脏、骨髓细胞和血液白细胞的影响。通过暴露于 MMS 后 1、6 和 18 小时彗星尾巴中的 DNA 含量(TDNA,%)来评估 DNA 损伤。BP-C2 在 20、200 和 2000mg/kg 的剂量下在大鼠的测试组织中没有表现出遗传毒性活性。BP-C2 在 MMS 前 1 小时以 20、100 和 200mg/kg 的剂量给药可显著(p<0.01)减轻 MMS 诱导的 DNA 损伤,在肝脏中表现出强烈的遗传保护作用。在接受 BP-C2 治疗的动物的血液白细胞和骨髓样本中,TDNA% 略高于阴性对照(载体),但明显低于阳性对照(MMS)。因此,BP-C2 对 MMS 诱导的 DNA 损伤具有更强的遗传保护作用,对肝细胞的作用更为明显,需要进一步评估该物质作为遗传保护剂的效果。