Nakanomyo H, Hiraoka M, Shiraya M
J Toxicol Sci. 1986 Apr;11 Suppl 1:301-10. doi: 10.2131/jts.11.supplementi_301.
Mutagenicities of Etoposide (VP 16-213) and Teniposide (VM-26), podophyllotoxin derivatives with antitumor activity, were studied by Rec-assay, Salmonella/microsome reverse mutation assay (Ames' test) and Micronucleus test. In the Rec-assay, both Etoposide and Teniposide showed positive results on B. subtilis H17 rec+ and M45 rec-. They also induced the revertants of S. typhimurium TA 98, TA 1537 and TA 1538, but not of S. typhimurium TA 100, TA 1535 or E. coli WP2 uvrA in the Reverse mutation test. The results were not influenced by the addition of S-9 Mix. In the Micronucleus test, Etoposide and Teniposide induced significantly micronucleated polychromatic erythrocytes of the bone marrow cells in mice; 3.3-4.3% at the doses of 0.75-6 mg/kg and 4.0-6.1% at 0.5-4 mg/kg, respectively. These results indicate that Etoposide and Teniposide are both mutagenic.
通过Rec试验、沙门氏菌/微粒体回复突变试验(艾姆斯试验)和微核试验,研究了具有抗肿瘤活性的鬼臼毒素衍生物依托泊苷(VP 16 - 213)和替尼泊苷(VM - 26)的致突变性。在Rec试验中,依托泊苷和替尼泊苷对枯草芽孢杆菌H17 rec + 和M45 rec - 均呈阳性结果。在回复突变试验中,它们还诱导了鼠伤寒沙门氏菌TA 98、TA 1537和TA 1538的回复突变,但未诱导鼠伤寒沙门氏菌TA 100、TA 1535或大肠杆菌WP2 uvrA的回复突变。结果不受添加S - 9混合液的影响。在微核试验中,依托泊苷和替尼泊苷分别在0.75 - 6 mg/kg剂量下诱导小鼠骨髓细胞产生显著的微核多染红细胞,比例为3.3 - 4.3%;在0.5 - 4 mg/kg剂量下,比例为4.0 - 6.1%。这些结果表明依托泊苷和替尼泊苷均具有致突变性。