The work addresses the question of membranes's proteins modifications in carcinogenesis. It was shown that T-helper factor obtained as the supernatant of a cultured thymome of T-helper lymphocytes could inhibit DNA synthesis in murine B leukemias transformed by Abelson's virus. In 7 cell lines of Abelson's murine leukemia studied the effect was quantified and shown to be identical to that of LPS, another cell growth factor of normal B cells. The results obtained point to qualitative modifications in transformed cells of membrane receptors to growth factors. To further clarify the role of qualitative vs. quantitative alterations in membrane's proteins a system was devised and developed to evaluate the action of mutagens/carcinogens in vitro on a gene encoding a membrane's protein, cloned in a vector plasmid. two recombinant plasmids were genetically engineered containing the lamB gene of E. coli under lac control. The physical map of the 2 plasmids-pJR11 and pJR21 - was established and pJR21 was chosen for the in vitro mutagenesis studies. pJR21 was previously characterized with respect to the expression of the cloned gene, its regulation and recombination with chromosomal DNA. The carcinogen ethyl-methane-sulphonate was used as the alkylating agent in vitro for pJR21. Four mutants were characterized for the transmembrane transport of maltose and dextrins and for ligation to phages lambda, lambdah, lambda hh** and K10. The obtained results suggest that alterations not hampering the location of the protein in the membrane can modify the response to ligands of the receptor. These data agrees with the hypothesis that point mutations in genes of membrane's proteins can modify ligand's activity and be involved in the process of carcinogenesisAvailable from Fundacao para a Ciencia e a Tecnologia, Servico de Informacao e Documentacao, Av. D. Carlos I, 126, 1200 Lisboa / FCT - Fundação para o Ciência e a TecnologiaSIGLEPTPortuga
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