Comparison of Transcriptomics Changes Induced by TCS and MTCS Exposure in Human Hepatoma HepG2 Cells

Triclosan (TCS) has been a widely used antibacterial agent in medical
and personal care products in the last few decades. Methyl TCS (MTCS)
is the major biotransformation product of TCS through replacement
of the hydroxyl group with methoxy. Previous studies revealed that
MTCS showed reduced toxicity but enhanced environmental persistence,
when compared with TCS. Till date, the toxicological molecular mechanisms
of TCS and MTCS remain to be clarified. This study aimed to investigate
the transcriptomic changes in HepG2 cells induced by TCS and MTCS
using microarray chips and to identify key target genes and related
signal pathways. The microarray data showed that there were 1664 and
7144 differentially expressed genes (DEGs) in TCS- and MTCS-treated
groups, respectively. Gene ontology (GO) enrichment and Kyoto Encyclopedia
of genes and genomes (KEGG) analysis revealed that TCS and MTCS induced
overlapping as well as distinct transcriptome signatures in HepG2
cells. Both TCS and MTCS could result in various biological responses
in HepG2 cells mainly responding to biosynthetic and metabolic processes
but probably through different regulatory pathways. Among the selected
50 GO terms, 9 GO terms belonging to the cellular component category
were only enriched in the MTCS group, which are mainly participating
in the regulation of cellular organelle’s function. KEGG analysis
showed that 19 and 59 pathway terms were separately enriched in TCS
and MTCS groups, with only seven identical pathways. The selected
10 TCS-specific signal pathways are mainly involved in cell proliferation
and apoptosis, while the selected 10 MTCS-specific pathways mainly
take part in the regulation of protein synthesis and modification.
The overall data suggested that MTCS induced more enriched DEGs, GO
terms, and pathway terms than TCS. In conclusion, compared with TCS,
MTCS presents lower polarity and stronger lipophilicity, enabling
MTCS to cause more extensive transcriptomic changes in HepG2 cells,
activate differentiated signal pathways, and finally lead to differences
in biological responses.