关键词: apoptosis chromium(III) chromium(VI) exposure pathway and duration micronuclei pregnant females transplacental genotoxicity

Mesh : Mice Male Female Pregnancy Animals Mice, Inbred ICR Chromium / toxicity Erythrocytes Micronucleus Tests

来  源:   DOI:10.1002/jat.4556

Abstract:
This study investigated the genotoxic effects of chromium (Cr) in Hsd:ICR mice, considering factors such as oxidative state, apoptosis, exposure pathway, duration, pregnancy, and transplacental exposure. Genotoxicity was assessed using the erythrocytes\' micronucleus (MN) assay, while apoptosis was evaluated in nucleated blood cells. The results showed that Cr(III) (CrK(SO4 )2 and CrCl3 ) did not induce any marked genotoxic damage. However, Cr(VI) (CrO3 , K2 Cr2 O7 , Na2 Cr2 O7 , and K2 CrO4 ) produced varying degrees of genotoxicity, with CrO3 being the most potent. MN frequencies increased following 24-h exposure, with a greater effect in male mice. Administering 20 mg/kg of CrO3 via gavage did not lead to significant effects compared to intraperitoneal administration. Short-term oral treatment with a daily dose of 8.5 mg/kg for 49 days elevated MN levels only on day 14 after treatment. Pregnant female mice exposed to CrO3 on day 15 of pregnancy exhibited reduced genotoxic effects compared to nonpregnant animals. However, significant increases in MN levels were found in their fetuses starting 48 h after exposure. In summary, data indicate the potential genotoxic effects of Cr, with Cr(VI) forms inducing higher genotoxicity than Cr(III). These findings indicate that gender, exposure route, and pregnancy status might influence genotoxic responses to Cr.
摘要:
这项研究调查了铬(Cr)在Hsd:ICR小鼠中的遗传毒性作用,考虑到氧化状态等因素,凋亡,暴露途径,持续时间,怀孕,和胎盘暴露。使用红细胞微核(MN)测定法评估遗传毒性,而在有核血细胞中评估细胞凋亡。结果表明,Cr(III)(CrK(SO4)2和CrCl3)没有引起任何明显的遗传毒性损伤。然而,Cr(VI)(CrO3,K2Cr2O7,Na2Cr2O7,和K2CrO4)产生不同程度的遗传毒性,CrO3是最有效的。MN频率在24小时暴露后增加,对雄性小鼠有更大的影响。与腹膜内施用相比,通过管饲法施用20mg/kg的CrO3不会导致显著的效果。每日剂量8.5mg/kg的短期口服治疗49天,仅在治疗后第14天提高了MN水平。与非怀孕动物相比,在怀孕第15天暴露于CrO3的怀孕雌性小鼠表现出降低的遗传毒性作用。然而,从暴露后48小时开始,胎儿的MN水平显着增加。总之,数据表明Cr的潜在基因毒性作用,与Cr(VI)形成比Cr(III)诱导更高的遗传毒性。这些研究结果表明,性别,暴露途径,妊娠状态可能会影响对Cr的遗传毒性反应。
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