Comparison of the effects of hydrogen peroxide and X-ray irradiation on toxicity, mutation, and DNA damage/repair in mammalian cells (V-79)

Cyclic amino acid derivatives

41 compounds or mixtures of diverse structure and application have been tested for genotoxic activity. The materials were tested in bacterial mutation assays, in Saccharomyces cerevisiae JD1 for mitotic gene conversion and in a cultured rat-liver cell line for structural chromosome damage. 11 compounds were bacterial mutagens, 4 induced mitotic gene conversion in yeast and 5 were positive in the chromosome assay. 5 of the materials were positive in bacteria only and 2 compounds induced chromosome damage in cultured cells in the absence of mutation in bacteria or gene conversion in yeast. The materials were tested over a 5-year period and the performance and evolution of the 3 assays during this time is evaluated. The results are considered in relation to the structure of the chemicals and the genotoxicity of related compounds.

Genetic toxicology testing of 41 industrial chemicals.

Longevity, stability and DNA repair.

Publisher Summary This chapter reviews eight years of mammalian cell studies performed by the radiobiology group of Atomic Energy of Canada Ltd., Pinawa, with emphasis on the time scale of radiation-induced events. It reviews this information with other recent studies relating to radiation mechanisms and their time scale. The chapter discusses several concepts currently isolated in separate publications and presents a framework for understanding mechanisms of radiation events in mammalian cells. The chapter discusses the time scale of critical events that may provide a more appropriate conceptual framework for teaching radiation biology, especially to graduate students, than does the usual historical approach. Furthermore, the chapter describes the performance of experiments designed to test some of the mechanisms proposed. It also discusses some implications of these mechanisms for radiation oncology and for the assessment of acceptable radiation exposure limits. It further describes some studies that attempt to define some major pathways that result in radiation-induced loss of cellular proliferative capacity. These are proposed as first approximations to the mechanisms that contribute to proliferative cell death and perhaps to other endpoints.

Radiation-Induced Events and Their Time Scale in Mammalian Cells

For purposes of studying stereostructure-activity relationships at the molecular, cellular, and animal levels and probing the mechanism of 2-mercaptoethylamine (MEA) radioprotection we synthesized several conformationally constrained cyclobutyl analogs. The comparative radioprotective properties for MEA, cis- and trans-2-mercaptocyclobutylamine (2), cis- and trans-2-mercaptocyclobutylmethylamine (3), and trans-2-mercaptomethylcyclobutylamine (4) are discussed in terms of their ability to chemically reduce transient free radicals, the formation of single strand breaks in DNA, and protect Chinese hamster cells (in vitro) and mice against the lethal effects of ionizing radiation. The results are interpreted in light of current proposed mechanisms of action for MEA. No correlation exists between ability of these analogs to enhance mice survival times and their ability to protect against the induction of DNA single strand breaks and the inactivation of proliferative capacity of hamster cells growing in vitro. Analysis of two isomers (cis- and trans-3) on the repair of single strand breaks showed both isomers only marginally influenced the rate and did not influence of extent of single strand break rejoining. The results are consistent with a mode of action involving chemical repair of transient radicals and protection against DNA and critical enzymatic sites.

Radioprotective stereostructure-activity study of cis- and trans-2-mercaptocyclobutylamine analogs and homologs of 2-mercaptoethylamine

Pyrazole product ratio analysis of the reaction of diazomethane with methyl cis- and trans-beta-chloroacrylates.

cis- and trans-2-Mercaptocyclobutylamines. Synthesis and antilipolytic properties in vitro.

Cis- and trans-2-mercaptocyclobutylamines, their benzylmercapto analogs, and aminomethyl homologs. Influence on bradykinin-induced contraction of the guinea pig ileum.

Birandra K. Sinha

Papers

Radioprotective stereostructure-activity study of cis- and trans-2-mercaptocyclobutylamine analogs and homologs of 2-mercaptoethylamine

Pyrazole product ratio analysis of the reaction of diazomethane with methyl cis- and trans-beta-chloroacrylates.

cis- and trans-2-Mercaptocyclobutylamines. Synthesis and antilipolytic properties in vitro.

Cis- and trans-2-mercaptocyclobutylamines, their benzylmercapto analogs, and aminomethyl homologs. Influence on bradykinin-induced contraction of the guinea pig ileum.