METHODS: Male rats were given the hepatotoxicant methapyrilene
at two dose levels, with livers and kidneys removed 24 hr after one, three, and seven doses for gene expression analysis.
It is methapyrilene
and was sold under the trade names Co-Pyronil and Histadyl EC.
That has only happened three times in the past 25 years: in 1977 with the antimicrobial hexachlorophene, in 1979 with the antihistamine methapyrilene
and in 1978 with the laxative danthron.
2004) and of rat hepatic gene expression changes induced by methapyrilene
(Waring et al.
That happened in 1977 with the antimicrobial hexachlorophene, two years later with the antihistamine methapyrilene
and again in 1987 with danthron, a laxative.
We evaluated gene expression patterns from cultured rat primary hepatocytes after a 24-hr incubation with methapyrilene
Statistical analyses of a methapyrilene
study vividly demonstrate sources of "false discoveries" (Chapter 6).
These results are consistent with those of a previously reported study where methapyrilene
toxicity correlated with the severity of pathologic changes (Hamadeh et al.
Interlaboratory evaluation of rat hepatic gone expression changes induced by methapyrilene
. Environ Health Perspect 112:439-448.
In this study we used quantitative reverse transcription-polymerase chain reaction (qRT-PCR) to investigate discrepant results between the National Institute of Environmental Health Sciences cDNA and Affymetrix oligo platforms used to evaluate hepatic gene expression changes in rats exposed to methapyrilene
. Caldesmon cDNA platform hybridization results showed decreases in gene expression levels for the high-dose methapyrilene
7-day pooled samples compared with their controls.
The Hepatotoxicity Working Group of the International Life Sciences Institute Health and Environmental Sciences Institute consortium on the application of genomics to mechanism-based risk assessment is investigating these factors by comparing high-density gene expression data sets generated on two sets of RNA from methapyrilene
(MP) experiments conducted at Abbott Laboratories and Boehringer-Ingdheim Pharmaceuticals, Inc.
To address this question, several members of the Hepatotoxicity Working Group of the International Life Sciences Institute Health and Environmental Sciences Institute evaluated the liver gene expression profiles of rats treated with methapyrilene