Frederick De Serres – författare

This book is concerned with the genetic consequences of nu­ cleotide pool imbalance. There are a number of ways in which this state can be achieved and the majority of papers in this volume de­ scribe the effects of nucleotide pool imbalance on DNA replication and repair, and the induction of gene mutations in various organisms. This book grew out of a Conference on "Genetic Consequences of Nu­ cleotide Pool Imbalance" which was held at the National Institute of Environmental Health Sciences on May 9-11, 1983. The Organizing Com­ mittee consisted of Drs. Diana Anderson (BIBRA), Robert Haynes (York University), Bernard Kunz (NIEHS), Barry Glickman (NIEHS), and Frederick J. de Serres (NIEHS), Chairman. The meeting was org- ized by the staff of the Office of the Associate Director for Genetics and was financed solely by the National Institute of Environmental Health Sciences. Frederick J. de Serres, Ph.D. Associate Director for Genetics v CONTENTS SECTION I. INTRODUCTION Molecular Mechanisms in Genetic Stability and Change: 1 The Role of Deoxyribonucleotide Pool Balance •••••• Robert H. Haynes SECTION II. NUCLEOTIDE METABOLISM 25 Metabolic Effects of Poly(ADP-ribose) Inhibitors •••••••• Kathryn M. Milam and James E. Cleaver Ribonucleotide Reductase and Deoxyribonucleotide 33 POQ 1 s ............................................ . Peter Reichard 47 Enzymatic Channeling of DNA Precursors •••••••••••••••••• Christopher K. Mathews A Possible Secondary Role for Thymine-Containing DNA 67 Precursors ....................................... . Robert J. Melamede and Susan S. Wallace Multiple Mechanisms of Adenosine Toxicity in an Adenosine Sensitive Mutant of Baby Hamster 103 Kidney (BHK) Cells............................... .

This book is concerned with the genetic consequences of nu­ cleotide pool imbalance. There are a number of ways in which this state can be achieved and the majority of papers in this volume de­ scribe the effects of nucleotide pool imbalance on DNA replication and repair, and the induction of gene mutations in various organisms. This book grew out of a Conference on "Genetic Consequences of Nu­ cleotide Pool Imbalance" which was held at the National Institute of Environmental Health Sciences on May 9-11, 1983. The Organizing Com­ mittee consisted of Drs. Diana Anderson (BIBRA), Robert Haynes (York University), Bernard Kunz (NIEHS), Barry Glickman (NIEHS), and Frederick J. de Serres (NIEHS), Chairman. The meeting was org- ized by the staff of the Office of the Associate Director for Genetics and was financed solely by the National Institute of Environmental Health Sciences. Frederick J. de Serres, Ph.D. Associate Director for Genetics v CONTENTS SECTION I. INTRODUCTION Molecular Mechanisms in Genetic Stability and Change: 1 The Role of Deoxyribonucleotide Pool Balance •••••• Robert H. Haynes SECTION II. NUCLEOTIDE METABOLISM 25 Metabolic Effects of Poly(ADP-ribose) Inhibitors •••••••• Kathryn M. Milam and James E. Cleaver Ribonucleotide Reductase and Deoxyribonucleotide 33 POQ 1 s ............................................ . Peter Reichard 47 Enzymatic Channeling of DNA Precursors •••••••••••••••••• Christopher K. Mathews A Possible Secondary Role for Thymine-Containing DNA 67 Precursors ....................................... . Robert J. Melamede and Susan S. Wallace Multiple Mechanisms of Adenosine Toxicity in an Adenosine Sensitive Mutant of Baby Hamster 103 Kidney (BHK) Cells............................... .

Frederick J. de Serres, Ph. D. Office of the Associate Director for Genetics National Institute of Environmental Health Sciences Research Triangle Park, North Carolina (U. S. A. ) 27709 The Workshop on Comparative Chemical Mutagenesis was orga­ nized to begin the process of problem identification and resolution concerning our needs to evaluate the data on test chemicals arising from assays for mutagenic activity on laboratory organisms. In the past, data on chemical mutagens has been generated and published in the scientific literature on a more or less random basis. Individual chemicals enjoy a brief period of "popularity" that leads to a burst of publications in the same or sometimes related assay systems. The incompleteness of the data base, in many of these cases, makes comparative mutagenesis difficult or impossible. In our attempts to compare the genetic effects of a given chemical over a wide range of assay systems, we are often interested in making quantitative as well as qualitative compari­ sons. To restate the first comparison: is the chemical under ques­ tion a weak, moderate or potent mutagen over a wide range of assay systems--or alternatively, does the level of response vary markedly? To make the second comparison, what is needed is information on the spectrum of genetic alterations produced as well as whether this spectrum is consistent over a wide range of organisms.