The crucial role of M-CSF on osteoclastogenesis was further supported by the study on the naturally occurring 'toothless' mutation in rat which was found to be due to the mutation of the Csf1 (M-CSF) gene [10].
Our results corroborate earlier biochemical work demonstrating the high functional importance of Helix 0. Specifically, in the liposome assay, F10E (the mutation in rat endophilin that is homologous to I10E) severely reduces lipid binding and disrupts tubulation [9], [14].
In addition, acrylamide may induce carcinogenesis and heritable mutations in rats when orally administrated in high-dose experiments in laboratory, which implies that it is probably carcinogenic to humans [ 5, 6].
Exposure to N-nitrosamino compounds was associated with G : C → A : T transitions in the RAS gene in tumours of rodents (Harris, 1991) and also with VHL mutations in rats (Shiao et al, 1998).
The maximum ENU-induced mutation rate in rats is approximately one point mutation every 1.25 – 1.5 Mb for Wistar rats treated with 35 40 mg ENU per kg bodyweight [ 5], which is similar to the highest mutation frequency that can be obtained in mice [ 8- 12].
In addition, we elucidated the mutational fingerprints of Phlp by analyzing Apc mutations in rat colon cancers induced by this carcinogen.
Motif mutation studies in rats have indicated that nuclear respiratory factor 1 (NRF-1), NRF-2 and Sp1 promote basal Tfam gene transcription.
APM was not genotoxic in the following tests: dominant lethal mutation assay in rats, host-mediated assay in rats and mice, in vivo cytogenetic assay in rats, and the Ames test (Kotsonis and Hjelle 1996).
The point mutations in rat PAR3 cDNA were introduced with QuikChange™ Site-Directed Mutagenesis Kit (Stratagene).
CRCs develop from normal colonic mucosa via progressive accumulation of genetic alterations, such as mutations in adenomatous polyposis coli (APC) during earlier stages and mutations in rat sarcoma viral oncogene homolog (RAS) and tumor protein 53 (TP53) during later stages [ 4].
