Pfeiffer E, Gross K, Metzler M
Institute of Food Chemistry, University of Karlsruhe, Germany.
Carcinogenesis. 1998 Jul;19(7):1313-8. doi: 10.1093/carcin/19.7.1313.
The aneuploidogenic and clastogenic potentials of the mycotoxins citrinin (CIT) and patulin (PAT) were studied by determining inhibition of microtubule assembly under cell-free conditions and by measuring induction of mitotic arrest and micronuclei in cultured Chinese hamster V79 cells. Both CIT and PAT inhibited cell-free microtubule polymerization in a concentration-dependent manner. PAT, but not CIT, bound covalently to reactive thiol groups of microtubule proteins. At concentrations without gross cytotoxicity, mitotic arrest and CREST-positive micronuclei, i.e. micronuclei containing whole chromosomes/chromatids, were induced by CIT and PAT in V79 cells. The time course of micronucleus induction and positive CREST staining indicate the aneuploidogenic potential of CIT and PAT. CREST-negative micronuclei, i.e. micronuclei containing acentric chromosomal fragments, were induced by PAT but not by CIT, implying a clastogenic potential of PAT. The aneuploidogenic and clastogenic potential of PAT and the aneuploidogenic potential of CIT may well contribute to the putative carcinogenicity of these mycotoxins in long-term animal studies.
通过在无细胞条件下测定微管组装抑制情况以及在培养的中国仓鼠V79细胞中测量有丝分裂停滞和微核诱导情况，研究了桔霉素（CIT）和展青霉素（PAT）这两种霉菌毒素的非整倍体形成和致断裂潜力。CIT和PAT均以浓度依赖方式抑制无细胞微管聚合。PAT而非CIT与微管蛋白的反应性巯基共价结合。在无明显细胞毒性的浓度下，CIT和PAT在V79细胞中诱导了有丝分裂停滞和着丝粒蛋白（CREST）阳性微核，即含有整条染色体/染色单体的微核。微核诱导的时间进程和CREST阳性染色表明CIT和PAT具有非整倍体形成潜力。PAT诱导了CREST阴性微核，即含有无着丝粒染色体片段的微核，但CIT未诱导，这意味着PAT有致断裂潜力。PAT的非整倍体形成和致断裂潜力以及CIT的非整倍体形成潜力很可能在长期动物研究中促成了这些霉菌毒素的假定致癌性。
