title: Metallothionein colon crypt immuno-positivity as a rapid in vivo essay for drug efficacy studies.
abstract: Metallothionein immune positivity indices are considered as representative of crypt stem cell mutations. The frequency and size of MT- immunopositive foci, as well as the total number of MT-immunopositive crypts were assessed here in a short term in vivo assay. Drug efficacy was tested on early mutated crypts in colon of Balb-c mice 30 days after induction with a single dose of the mutagen dimethylhydrazine. The different drugs used (MS 275, vioxx, 5-fluorouracil, aminophylline, 5-azadeoxycytine) affected the metallothionein - immunopositive crypt frequency according to their predicted efficacy on this specific model of mouse colon carcinogenesis. This preliminary validation study of metallothionein - immunopositive crypt frequency strengthens the evidence that metallothionein immunopositivity indices could be used as short-term markers to assess the capability of different pro-drugs to counteract crypt invasion and clonal expansion of mutated stem cell progeny. This rapid in vivo test (30 days) based on metallothionein immunopositivity indices can be assayed in paraffin-fixed tissue sections and has been validated against the Glucose 6 phosphate Dehydrogenase assay. To quantify metallothionein immunopositivity indices, we devised a novel fast analysis protocol based on the Zeiss Axiovision software for image processing.
authors: IFO Istituto Fisioterapico Ospedaliero, Rehabilitation and Physiotherapeutic Clinical Center, National Cancer Institute Regina Elena, Rome, Italy.
authors: Federica
authors: F
authors: Mori
authors: Carlo
authors: C
authors: Della Rocca
authors: Domenico
authors: D
authors: Lazzaro
mesh_terms: D000818:Animals; D003106:Colon / Q000378:metabolism*; D004358:Drug Therapy; D008297:Male; D008668:Metallothionein / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D016612:Paraffin Embedding
chemical_list: D008668:Metallothionein