Developmental neurotoxicity of chlorpyrifos: cellular mechanisms

Toxicology and Applied Pharmacology
K D WhitneyTheodore A Slotkin

Abstract

Chlorpyrifos, one of the most widely used pesticides, exhibits greater toxicity during development than in adulthood. We administered chlorpyrifos to neonatal rats in apparently subtoxic doses that caused no mortality and little or no weight deficits and examined developing brain regions (cerebellum, forebrain, brainstem) for signs of interference with cell development. One-day-old rats given 2 mg/kg sc of chlorpyrifos showed significant inhibition of DNA synthesis in all brain regions within 4 hr of treatment; equivalent results were obtained when a small dose (0.6 microgram) was introduced directly into the brain via intracisternal injection, indicating that the actions were not secondary to systemic toxicity. Inhibition of DNA synthesis was also seen at 8 days of age; however, at this point, there was regional selectivity, with sparing of the cerebellum. Between 1 and 8 days of age, brain regions develop wide disparities in cholinergic innervation; accordingly, we tested whether the effect of chlorpyrifos was mediated through cholinergic actions on nicotinic receptors known to mediate inhibition of DNA synthesis. Pretreatment with mecamylamine caused a decline in DNA synthesis by itself, but nevertheless prevented the effect...Continue Reading

Citations

Sep 27, 2001·Archives of Environmental Health·J D Thrasher, K H Kilburn
Jan 1, 2003·Archives of Environmental Health·Jack D ThrasherAlan Broughton
Sep 17, 2004·Journal of Toxicology and Environmental Health. Part a·S PadillaV C Moser
Jun 16, 2011·Toxicological Sciences : an Official Journal of the Society of Toxicology·Toby B ColeClement E Furlong
Feb 17, 2000·Annals of the New York Academy of Sciences·P J Landrigan
Jun 16, 2000·Environmental Health Perspectives·R A FenskeM C Keifer
Nov 6, 2002·Environmental Health Perspectives·Dan QiaoTheodore A Slotkin
Mar 14, 2003·Environmental Health Perspectives·Annemarie WasleyCarol Rubin
Sep 7, 2007·Environmental Health Perspectives·Theodore A SlotkinFrederic J Seidler
Mar 13, 2008·Environmental Health Perspectives·Theodore A SlotkinFrederic J Seidler
Feb 3, 2004·Environmental Health Perspectives·Philip J LandriganBrenda Eskenazi
Mar 5, 2004·Environmental Health Perspectives·Gertrud S BerkowitzMary S Wolff
Dec 4, 2003·Environmental Health Perspectives·Armando MeyerTheodore A Slotkin
Nov 5, 2003·Environmental Health Perspectives·Justin E AldridgeTheodore A Slotkin
Oct 6, 2005·Environmental Health Perspectives·Theodore A SlotkinFrederic J Seidler
May 26, 1999·Environmental Health Perspectives·P J LandriganR W Amler
May 7, 1999·Environmental Health Perspectives·S Brimijoin, C Koenigsberger
May 7, 1999·Environmental Health Perspectives·T A Slotkin
May 29, 1999·Environmental Health Perspectives·B EskenaziR Castorina
May 29, 1999·Environmental Health Perspectives·P J LandriganM S Wolff
Feb 28, 2013·International Journal of Molecular Sciences·Lara BoattiFrancesco Marsano

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.