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The role of dna repair in tumour resistance to anti-cancer agents using dna repair gene 'knock-out' xenografts in syngeneic rats


A number of eukaryotic, in part human genes involved in the repair of different DNA lesions have been cloned and are currently being used to define the role of DNA repair mechanisms in carcinogenesis and in tumour response to chemotherapy. This project would involve the study of the gene encoding the O6-alkylguanine-DNA alkyltransferase (AT), which appears to be of primary biological importance. The AT gene would be inactivated ("null-mutation") by homologous recombination in a number of tumourigenic cell lines from the BDIX rat which would subsequently be transplanted into syngeneic animals. Following exposure to chemotherapeutic alkylating agents, the formation and repair of DNA lesions could then be measured in wild-type, heterozygous and homozygous null-mutant cells in the same animal, and the effects on tumour cell sensitivity could be compared.

Funding Scheme

RGI - Research grants (individual fellowships)


Universität Gesamthochschule Essen
Hufelandstraße 55
45147 Essen

Participants (1)

Not available
United Kingdom