Clastogenic, aneugenic, and tubulin polymerization properties of di-(2-ethylhexyl) phthalate and dibutyl phthalate

Abstract

Phthalate compounds were found to disrupt the endocrine system and alter transcriptomes during human embryonic development. In our previous work, we have isolated and reported two such phthalates di-(2-ethylhexyl) phthalate (DEHP) and dibutyl phthalate (DBP) from Brevibacterium mcbrellneri bacteria and evaluated their bioactive properties. Naturally derived phthalates might be less toxic compared with synthesized molecules. We have investigated biologically isolated phthalates to understand the possible genotoxic effects in mice and further investigated in silico binding and polymerization of β-tubulin. Three sub-lethal concentrations of DEHP (150 μM, 175 μM, and 200 μM) and DBP (10 μM, 15 μM, and 30 μM) were studied. The results showed that the phthalates were found to be highly genotoxic in nature. However, the pattern of genotoxic effects was not found to be dose-dependent in the induction of chromosome aberrations (CA), micronuclei (MN), and changes in the mitotic index (MI) in cells. In silico studies of phthalates on polymerization of β-tubulin suggested that both DBP and DEHP were able to interact with the hydrogen bonds and make strong van der Waals interactions with β-tubulin thereby possibly causing destabilization of microtubule network. Our study suggests that these phthalates might be playing an important role in normal cell division thereby showing highly genotoxic effects.