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Clastogenic Effects of Two Tyrosine Kinase Inhibitors, Tyrphostin 23 and Tyrphostin 46, on a Transformed (CHO-K1) and on a Primary Embryonic Chinese Hamster Cell Line (CHE)

Clastogenic Effects of Two Tyrosine Kinase Inhibitors, Tyrphostin 23 and Tyrphostin 46, on a Transformed (CHO-K1) and on a Primary Embryonic Chinese Hamster Cell Line (CHE)

L Bassi, R Buzzi, M Fiore, F Palitti

Mutagenesis. 2000 Jul;15(4):341-7.

PMID: 10887214

Abstract:

Protein tyrosine kinases (PTKs) play fundamental roles in signal transduction pathways. Many proliferative diseases are characterized by deregulation of PTK activity, therefore PTKs appear as promising targets in the design of anticancer drugs. Tyrphostins are a family of synthetic compounds which efficiently target specific PTKs without competing for ATP and thus are much less cytotoxic with respect to conventional therapeutic agents. We tested two tyrphostin derivatives, Tyrphostin 23 and Tyrphostin 46, on a transformed (CHO-K1) and on a primary embryonic Chinese hamster cell line (CHE) to determine whether these compounds had a genotoxic effect. We found that the tyrphostins increased sister chromatid exchange frequency in both cell lines, but induced chromosomal aberrations only in the transformed CHO-K1 cell line when treatment was in the S phase of the cell cycle, and not in primary CHE cells. Such a result could have important therapeutic implications: it could mean that deregulation of signal transduction pathways in cells which already have a deficit in cell cycle control could cause chromosomal aberrations.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP118409577-B	Tyrphostin 23		118409-57-7	Price

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