Methapyrilene, an antihistaminic compound removed from the U.S.
Thus, to facilitate the identification of toxicity-related genes, we compared gene changes in a nontarget tissue for toxicity--the kidney--with those of the target organ of methapyrilene toxicity--the liver--in addition to analyzing gene expression changes across dose level and number of doses.
In brief, we dosed male Sprague-Dawley (Charles River Laboratories, Kingston, NY) rats for one, three, or seven daily doses by gavage with vehicle (water), 10 mg/kg/day methapyrilene, or 100 mg/kg/day methapyrilene (n = 4 rats per dose group).
Morphology of early changes in liver carcinogenesis induced by methapyrilene. Arch Toxicn149:79-83.
Examination of genotoxicity, toxicity and morphologic alterations in hepatocytes following in vivo or in vitro exposure to methapyrilene. Carcinogenesis 9:959-963.
This 74-bp sequence is completely homologous with the alpha-2 microglobulin accession number X14552 and J00738 sequences, qRT-PCR of an amplicon overlapping this 74-bp sequence, as well as for the alpha-2 microglobulin sequences X14552 and J00738, showed a substantial reduction (> 100-fold) in message levels for the day 7 high-dose methapyrilene sample, whereas a similar analysis of amplicons designed for the amplification of U18419 and AL180288 showed induction levels above 5-fold (Figure 2).
qRT-PCR data in Figures 2 and 3 suggest a possible explanation for the discrepancy between the NIEHS and Affymetrix platform results for the day 7 high-dose methapyrilene sample.
2004) to have reduced expression levels (5- and 7-fold, respectively) for the day 7 high-dose methapyrilene sample compared with its baseline expression levels.
Number of genes regulated by methapyrilene across the different companies in the pooled and individual samples at the high dose.
A study of the potential genotoxicity of methapyrilene and related antihistamines using the hepatocyte/DNA repair assay.
Methapyrilene was administered at 0, 10 or 100 mg/kg/day by gavage for 1, 3, and 7 days (Abbott Laboratories; Boehringer-Ingelheim Pharmaceuticals, Inc., Ridgefield, CT).
Histopathological and clinical chemistry observations on the methapyrilene-exposed animals were consistent with expected toxicities associated with methapyrilene treatment.