Effect of Trimethyltin chloride on proliferation and cell cycle of intestinal porcine epithelial cells

Comp Biochem Physiol C Toxicol Pharmacol. 2021 Nov:249:109131. doi: 10.1016/j.cbpc.2021.109131. Epub 2021 Jul 8.

Abstract

Trimethyltin chloride (TMT) is a highly toxic substance produced by organotin heat stabilizers in the synthesis of polyvinyl chloride (PVC) products. TMT is widely used in industry and agriculture. The aim of this study was to investigate the effects of TMT-induced cytotoxicity in intestinal porcine epithelial cells (IPEC-J2). Our study showed that TMT induced a decline in cell viability of IPEC-J2, caused cell shrinkage and rounded cell morphology, reduced the number of proliferating cells and the expression of proliferating cell nuclear antigen (PCNA), and increased lactate dehydrogenase (LDH) activity in cell supernatants. Simultaneously, TMT lowered the mRNA expression of Cyclin B1, and Cyclin D1, but increased P21 and P27 expression. The cell cycle progression was arrested from the G1 to the S phase. Furthermore, the mRNA expression of Bax/Bcl-2 ratio and the protein expression of cleaved Caspase-9 and cleaved Caspase-3 were significantly increased after TMT treatment, while the ratio of advanced apoptotic cells was elevated. These results indicated that TMT blocked the cell cycle, inhibited IPEC-J2 proliferation, and induced apoptosis.

Keywords: Cell cycle; Intestinal porcine epithelial cells; Proliferation; Trimethyltin chloride.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Cell Cycle / drug effects*
  • Cell Line
  • Cell Proliferation / drug effects
  • Epithelial Cells
  • Intestines / cytology
  • Intestines / drug effects*
  • Proteins / genetics
  • Proteins / metabolism*
  • Swine
  • Trimethyltin Compounds / toxicity*

Substances

  • Proteins
  • Trimethyltin Compounds
  • trimethyltin chloride