Abstract
Chromosome instability is a defining characteristic of most human cancer. Treatment with DNA damaging agents as well as epigenetic mechanisms increase the probability that whole chromosome or large fractions of chromosome are gained or lost during cell division. The major question of cancer genetics is to what extent chromosome instability, or any genetic instability, is an early event and consequently a driving force for tumor progression. Previously, we have shown that phenylhydroquinone (PHQ), hepatic metabolite of fungicide ortho-phenylphenol, can cause aneuploidy in Saccharomyces cerevisiae through binding to microtubulin and inhibiting tubulin-depolymerization. PHQ is known as non-mutagenic in standard gene mutation assays and does not bind nor cleave DNA. However, PHQ shows the increase in urinary bladder tumors in rats. Therefore, PHQ may exert its carcinogenic effect through attacking mitotic apparatus that causes aneuploidy.
In this study, we have further characterized effect of PHQ on human cell, HCT116. We found that 1) PHQ arrests cell cycle at mitosis, 2) PHQ causes aneuploidy, and 3) PHQ does not induce apoptosis. We therefore argue that PHQ causes chromosome instability by affecting cell cycle in human cell. We will discuss the possibility that aneuploidy is the cause but not the result of tumorigenesis.
