Impact of Environmental Chemicals on the Transcriptome of Primary Human Hepatocytes: Potential for Health Effects.
New paradigms for human health risk assessment of environmental chemicals emphasize the use of molecular methods and human-derived cell lines. In this study, we examined the effects of the insect repellent DEET (N,N-diethyl-m-toluamide) and the phenylpyrazole insecticide fipronil (fluocyanobenpyrazole) on transcript levels in primary human hepatocytes. These chemicals were tested individually and as a mixture. RNA-Seq showed that 100 μM DEET significantly increased transcript levels (α = 0.05) for 108 genes and lowered transcript levels for 64 genes and fipronil at 10 μM increased the levels of 2246 transcripts and decreased the levels for 1428 transcripts. Fipronil was 21-times more effective than DEET in eliciting changes, even though the treatment concentration was 10-fold lower for fipronil versus DEET. The mixture of DEET and fipronil produced a more than additive effect (levels increased for 3017 transcripts and decreased for 2087 transcripts). The transcripts affected for all chemical treatments were classified by GO analysis and mapped to chromosomes. The overall treatment responses, specific pathways, and individual transcripts affected were discussed at different levels of fold-change. Changes found in transcript levels in response to treatments will require further research to understand their importance in overall cellular, organ, and organismic function.
Department of Entomology, Toxicology Program, Department of Biology, North Carolina State University, Raleigh, NC, 27695, USA.
Robert D
RD
Mitchell
Department of Entomology, North Carolina State University, Raleigh, NC, 27695, USA.
Anirudh
A
Dhammi
Toxicology Program, Department of Biology, North Carolina State University, Raleigh, NC, 27695, USA.
Andrew
A
Wallace
Department of Applied Ecology, Toxicology Program, Department of Biology, North Carolina State University, Raleigh, NC, 27695, USA.
Ernest
E
Hodgson
Department of Entomology, Toxicology Program, Department of Biology, North Carolina State University, Raleigh, NC, 27695, USA. mroe@ncsu.edu.
R Michael
RM
Roe
D002874:Chromosome Mapping; D003671:DEET / Q000633:toxicity*; D004338:Drug Combinations; D015894:Genome, Human; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007302:Insect Repellents / Q000633:toxicity*; D007306:Insecticides / Q000633:toxicity*; D058977:Molecular Sequence Annotation; D061251:Primary Cell Culture; D011720:Pyrazoles / Q000633:toxicity*; D017423:Sequence Analysis, RNA; D059467:Transcriptome / Q000187:drug effects*
D004338:Drug Combinations; D007302:Insect Repellents; D007306:Insecticides; D011720:Pyrazoles; D003671:DEET; C082360:fipronil
DEET; Endocrine System; Fipronil; Gene expression; Human hepatocytes; P450; RNA-Seq