The multidrug resistance-associated protein 1 transports methoxychlor and protects the seminiferous epithelium from injury.

Abstract:

:We examined the ability of the multidrug resistance-associated protein 1 (MRP1/ABCC1) to transport pesticides, as this transporter mediates the cellular efflux of a variety of xenobiotics, typically as glucuronide, sulfate, or glutathione conjugates. NIH3T3 cells stably expressing MRP1 were 3.37-fold more resistant to the toxicity of fenitrothion, 3.12-fold more resistant to chlorpropham, and 2.5-fold more resistant to methoxychlor, a pesticide with estrogenic and anti-androgenic metabolites. The cells expressing MRP1 also eliminated methoxychlor two times more rapidly than their mock-transfected counterparts. We then examined whether mrp1 expression could alter the toxicity of methoxychlor in vivo using male FVB/mrp1 knockout mice (FVB/mrp1-/-). Both control and knockout mice were fed 25 mg/kg methoxychlor in honey for 39 days, and its effects on testicular morphology were examined. Methoxychlor treatment did not significantly affect testicular morphology in the FVB mice, but markedly reduced the number of developing spermatocytes in the FVB/mrp1-/- mice. These results suggest that MRPI may play a role in protecting the seminiferous tubules from methoxychlor-induced damage.

journal_name

Toxicol Lett

journal_title

Toxicology letters

authors

Tribull TE,Bruner RH,Bain LJ

doi

10.1016/s0378-4274(02)00485-x

keywords:

subject

Has Abstract

pub_date

2003-04-30 00:00:00

pages

61-70

issue

1-2

eissn

0378-4274

issn

1879-3169

pii

S037842740200485X

journal_volume

142

pub_type

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