Effects of sterol biosynthesis inhibitors on mitosis

The sterol biosynthesis inhibitors (SBIs) fenarimol, triadimenol, bitertanol, miconazole, clotrimazole, and fenpropimorph increase sectoring in a heterozygous diploid strain of Aspergillus nidulans, but only at concentrations highly inhibitory to growth. Analysis of color segregants suggest that SBIs cause chromosome nondisjunction. That fenarimol and clotrimazole disturb the mitotic process was also shown by cytological studies. In treated A. nidulans germ tubes it was impossible to observe the normal stages of mitotic division with the light microscope. At the electron microscope level, an abnormal nuclear division was observed, with a characteristic cross membrane dividing the nucleus into two unequal parts, with dissimilar chromatin content. In Chinese hamster cells, the two inhibitors increased the mitotic index and caused mitotic abnormalities such as chromosome clumping and chromatin fragmentation to more than two nuclear fragments. The mechanism of the genetic activity of SBIs is discussed and interference with the regulatory action of sterols is suggested.