Novel types of DNA-sugar damage in neocarzinostatin cytotoxicity and mutagenesis.

Abstract

Although a number of antitumor antibiotics interact with DNA1 to form physical complexes, or covalent adducts with the bases, relatively few damage DNA by specifically interacting with the deoxyribose moiety. Neocarzinostatin (NCS), a member of a family of macromolecular (Mr > 10,000) antibiotics obtained from culture filtrates of Streptomyces, is such an agent (for pertinent literature on NCS prior to 1980, see Ref. 2, and between 1980 and 1984, see Ref. 3). Many of the biochemical and cellular effects of NCS resemble those of ionizing radiation. Most, possibly all, of the DNA lesions caused by NCS appear to result from the direct attack of an activated form of the drug on the deoxyribose of DNA. This is to be contrasted with ionizing radiation or the antibiotic bleomycin, that damage DNA deoxyribose through the intervention of a reduced form of oxygen. This paper will describe current information on the nature of the interaction between the active component of NCS and DNA, on the mechanism of the ensuing deoxyribose damage, and on some of the biological consequences of these actions.