Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1998-11-16
pubmed:abstractText
We have completed 2 26-wk studies to evaluate the hemizygous transgenic Tg.AC mouse, which has been proposed as an alternative short term model for testing carcinogenicity. We attempted to evaluate the response to the known rodent carcinogens cyclophosphamide, phenolphthalein, and tamoxifen and to the noncarcinogen chlorpheniramine following topical application. In the first study, a weak response (2/17 animals) was observed to the positive control 12-O-tetradecanoylphorbol 13-acetate (TPA in ethanol, 1.25 micrograms), and no response was observed to cyclophosphamide, phenolphthalein, or chlorpheniramine, despite evidence for skin penetration. The second study compared 1.25 micrograms and 6.25 micrograms of TPA in ethanol and acetone solutions. Tamoxifen was also evaluated in both solvents and orally. No significant response was observed to tamoxifen by skin paint or oral routes. Over 60% of the high dose TPA-treated animals showed no (0 or 1) papilloma response, and 30% of the animals each developed more than 32 papillomas. The heterogenous response to high dose TPA may be related to variability in the responsiveness of hemizygous animals. In light of these findings, further Tg.AC studies should employ homozygous animals, and the underlying cause for heterogeneity in the tumorigenic response of Tg.AC mice should be identified and eliminated.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0192-6233
pubmed:author
pubmed:issnType
Print
pubmed:volume
26
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
532-40
pubmed:dateRevised
2009-7-1
pubmed:meshHeading
pubmed:articleTitle
An evaluation of the hemizygous transgenic Tg.AC mouse for carcinogenicity testing of pharmaceuticals. I. Evidence for a confounding nonresponder phenotype.
pubmed:affiliation
Office of Testing and Research, Food and Drug Administration, Laurel, Maryland 20708, USA.
pubmed:publicationType
Journal Article