Cancer a Comprehensive Treatise 2

Publisher Summary This chapter discusses some studies on the interaction of various compounds with cellular DNA and the biochemical and biological consequences of these reactions in a variety of cell systems and it focuses attention on DNA as the principal target for a number of chemotherapeutically useful cytotoxic agents and for numerous known carcinogens. The chapter further discusses some observations establishing that some DNA reactions are recognized and modified by various enzyme systems. These DNA repair processes clearly protect cells from lethal effects of DNA reactions in both bacterial and mammalian cells. Decreased sensitivity of sublines of cells in culture have been shown in some instances to be related either to their increased capacity for excision repair of damage to their DNA or to their greater capacity to carry out postreplication DNA repair. However, it is by no means established, although quite likely, that clinical resistance to cytotoxic agents in cancer chemotherapy is similarly characterized by the emergence of, or conversion of a tumor cell to, a cell with altered DNA repair capacity that confers decreased sensitivity to cytotoxic agents as compared with that of the original tumor cell.

The Repair of DNA Modified by Cytotoxic, Mutagenic, and Carcinogenic Chemicals

Summary Alkaline sucrose gradients were used to study the induction of single-strand breaks in and repair of rat liver DNA in vivo. Liver DNA was labeled during regeneration after partial hepatectomy. DNA was isolated from the organ in such a way as to minimize the induction of breaks due to handling or enzymatic activity. Different methods of preparing high-molecular-weight liver DNA were compared. Best results were obtained by squashing the liver in an ethylenediaminetetraacetic acid-sodium chloride buffer. Using this squash technique and alkaline sucrose gradients, high-molecular-weight DNA was regularly obtained. This DNA behaved like single-stranded DNA on hydroxyapatite columns and contained no detectable contamination of protein or RNA. It was demonstrated by the method described that hepatic DNA damage was produced within four hr by the administration of methyl methanesulfonate and that the rat can repair such hepatic DNA damage in vivo within 48 hr.

https://cancerres.aacrjournals.org/content/canres/33/9/2114.full.pdf

A method for measuring DNA damage and repair in the liver in vivo.

The genetic toxicology of nitrogen and sulphur mustard.

A sensitive method to measure physical and chemical carcinogen-induced "unscheduled DNA synthesis" in rapidly dividing eukaryotic cells.

The establishment of cloned cell lines from Yoshida sarcomas having differential sensitivities to methylene dimethane sulphonate in vivo and their cross-sensitivity to x-rays, UV and other alkylating agents.

Margaret Fox

Papers

The establishment of cloned cell lines from Yoshida sarcomas having differential sensitivities to methylene dimethane sulphonate in vivo and their cross-sensitivity to x-rays, UV and other alkylating agents.

Characteristics of repair synthesis in P388 cells treated with methyl methanesulphonate

The establishment of MDMS-resistant cloned cell lines from in vitro cultured, MDMS-sensitive, Yoshida sarcoma cells