E. Pfeiffer et al., ANEUPLOIDOGENIC AND CLASTOGENIC POTENTIAL OF THE MYCOTOXINS CITRININ AND PATULIN, Carcinogenesis (New York. Print), 19(7), 1998, pp. 1313-1318
The aneuploidogenic and clastogenic potentials of the mycotoxins citri
nin (CIT) and patulin (PAT) were studied by determining inhibition of
microtubule assembly under cell-free conditions and by measuring induc
tion of mitotic arrest and micronuclei in cultured Chinese hamster V79
cells. Both CIT and PAT inhibited cell-free microtubule polymerizatio
n in a concentration-dependent manner. PAT, but not CIT, bound covalen
tly to reactive thiol groups of microtubule proteins. At concentration
s without gross cytotoxicity, mitotic arrest and CREST-positive micron
uclei, i.e. micronuclei containing whole chromosomes/chromatids, were
induced by CIT and PAT in V79 cells. The time course of micronucleus i
nduction and positive CREST staining indicate the aneuploidogenic pote
ntial of CIT and PAT. CREST-negative micronuclei, i.e. micronuclei con
taining 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 mycotoxi
ns in long-term animal studies.