Atrazine exposure causes mitochondrial toxicity in liver and muscle cell lines.
OBJECTIVE
Chronic exposure to atrazine and other pesticides is reported to cause metabolic disorders, yet information on effects of atrazine on expression of genes relevant to mitochondrial function is largely missing. In the present study, therefore, we investigated the expression of a battery of nuclear- and mitochondrial-encoded genes involved in oxidative phosphorylation (OXPHOS) in human liver (HepG2) and rat muscle (L6) cell lines due to short-term atrazine exposure.


METHODS
We have determined the EC50 values of atrazine for cytotoxicity and mitochondrial toxicity (mitotoxicity) in terms of adenosine triphosphate (ATP) content in HepG2 and L6 cells. Further, the mRNA expression of nuclear- and mitochondrial-encoded genes was analyzed using quantitative real-time polymerase chain reaction.


RESULTS
The EC50 value of atrazine for mitotoxicity in HepG2 and L6 cells was found to be about 0.162 and 0.089 mM, respectively. Mitochondrial toxicity was indicated by reduction in ATP content following atrazine exposure. Atrazine exposure resulted in down-regulation of many OXPHOS subunits expression and affected biogenesis factors' expression. Most prominently, superoxide dismutase (SOD) and sirtuin 3 (SIRT3) expressions were up-regulated in HepG2 cells, whereas SIRT3 expression was alleviated in L6 cells, without significant changes in SOD levels. Mitochondrial transcription factor A (TFAM) and SIRT1 expression were significantly down-regulated in both cell lines.


CONCLUSIONS
Results suggest that TFAM and SIRT1 could be involved in atrazine-induced mitochondrial dysfunction, and further studies can be taken up to understand the mechanism of mitochondrial toxicity. Further study can also be taken up to explore the possibility of target genes as biomarkers of pesticide toxicity.
Environmental Genomics Division, CSIR-National Environmental Engineering Research Institute, Nagpur, India; Department of Biotechnology, Savitribai Phule Pune University, Pune, Maharashtra, India.
Sneha
S
Sagarkar
Environmental Health Division, CSIR-National Environmental Engineering Research Institute, Nagpur, India.
Deepa
D
Gandhi
Environmental Health Division, CSIR-National Environmental Engineering Research Institute, Nagpur, India.
S Saravana
SS
Devi
Department of Biotechnology, Savitribai Phule Pune University, Pune, Maharashtra, India.
Amul
A
Sakharkar
Environmental Genomics Division, CSIR-National Environmental Engineering Research Institute, Nagpur, India.
Atya
A
Kapley
D000818:Animals; D001280:Atrazine / Q000633:toxicity*; D002460:Cell Line; D056945:Hep G2 Cells; D006540:Herbicides / Q000633:toxicity*; D006801:Humans; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D008931:Mitochondria, Muscle / Q000187:drug effects* / Q000378:metabolism; D010085:Oxidative Phosphorylation; D051381:Rats
D006540:Herbicides; D001280:Atrazine
Gene expression; HepG2; L6; mitotoxicity