The Use of Human Cells for the Evaluation of Risk from Physical and Chemical Agents

In this volume are collected 30 papers, 9 round table discus­ sions and 11 communications presented at the ASI Course on "The use of human cells for the evaluation of risk from physical and chemical agents", sponsored by NATO and organized by ENEA. The aim of the Course was to present different scientific ap­ proaches and technical advices in order to get dose-effect relation­ ships which are the basis for risk evaluation. The scientific back­ ground which is behind this approach was extensively discussed. Emphasis has been given to the use of human cells or human data in order to attempt to have a correct and realistic evaluation of the damage in humans. There are many criticisms on the use of animal data for human risk evaluation because of differences between species and between strains within the same species: differences in metabolism, activa­ tion processes and DNA repair ability makes uncertain the extrapola­ tion of animal data to humans. Also data obtained using specific strains or highly inbred strains in order to reduce the variance are not applicable due to the heterogeneity of the human population connected with individual responses. In this respect only the use of human cells enable us to detect the individual variability and to identify sensitive subpopu­ lations that would be at greater risk. My appreciation to Pieranita and Alberto Castellani for the as­ sistance during the meeting and to Giuseppe Biondi for his help in some of the editorial work.

Lectures.- What do We Mean by the Expression Risk Assessment?.- The Search for Criteria to Assess the Risks Resulting from Exposure to Carcinogenic Agents.- Some Comments on the Use of Human Cells for Estimates of Risk.- The Strauss-Albertini Test for Direct Enumeration of Drug-Resistant Peripheral Blood Lymphocytes.- Induction of Sister Chromatid Exchange by Chemical Mutagens.- Dose-Response Relation of Chromosome Aberrations.- Mutagen-Induced Chromosome Damage in Man.- Repair of Radiation Damage in Mammalian Cells.- Repair and Expression of Aflatoxin B1-induced DNA Damage.- Parvoviral Probe for Assessing the Mutagenic Risk of Low Doses of Radiation and Chemicals Administered to Human Cells.- Assessment of Human Lymphoid Cell Damage Induced by Therapeutic Levels of 8-Methoxypsoralen and Long Wavelength Ultraviolet Radiation In Vitro.- The Mutagen Sensitivity Response of Cells from Individuals Heterozygous for DNA Repair Deficiency Genes.- Repair of Chemical Damage in Mammalian Cells.- Effects of Various Promoters on Cell Transformation by Simian Virus 40 Mutants.- Repair of Ultraviolet-Light-Induced Damage in Human Skin.- Dosimetry by Means of Measurement of Hemoglobin Alkylation and Risk Estimation Based on the rad-Equivalent Approach.- PUVA Therapy: Immunologic and Genotoxic Approaches to Risk Evaluation.- Parvoviral Probe of DNA Replication in Mammalian Cells Exposed to Genotoxic Agents.- Ultraviolet-Light-Induced Transformation of Human Primary Cells.- Use of Human Lymphoblastoid Cell Lines to Determine Cellular Hypersensitivty to Physical and Chemical Agents.- Cellular Studies on Patients with an Unusual Clinical Sensitivity to Ionizing Radiation.- Electrophilic Reactivity as a Measure of Genotoxic Potency.- SOS Functions Induced in Carcinogen-Treated Mammalian Cells.- Radiation-Induced Transformation in Rodent and Human Cells: Assay Systems and Uses in Risk Estimates.- Correlation of NCI and IARC Carcinogens with Their Mutagenicity in Salmonella.- A Review and Evaluation of Human Genetic Bioassay Data for Some Known or Suspected Human Carcinogens.- From Bacteria to Man, the Evolution of Mutagenicity Testing.- Genetic Bioassay Data on Some Known or Suspected Human Carcinogens.- The Search for Biological Models to Investigate Human Carcinogenic Risks: Human Pathology and Experimental Carcinogenesis Correlations at the Organ, Tissue and Cellular Level, In Vivo and In Vitro.- The Causes of Cancer: Quantitative Estimates of Avoidable Risks of Cancer in the United States Today.- Round Tables.- Reasons for Distrusting Human Risk Assessment Based Solely on In Vitro or Animal Test Results.- Quantitative Relationships, if Any, Between Human and Animal Carcinogenesis: Biological Aspects.- Qualitative and Quantitative Problems in the Extrapolation of Risk to Humans from Animal Data.- Risks from Ambient Chemicals and Radiations.- Human and Other Mammalian Cells: Their Role in Risk Assessment.- Measurements of DNA Repair Activity in Human Cells.- Risk Assessment for Low-Dose and Low-Dose-Rate Radiation.- Difference in Cancer Susceptibility among Individuals and What Determines the Differences.- Calibration and Monitoring of Human Population: Biological Aspects, Hemoglobin Alkylation and Radiation Equivalent Approach.- Communications.- Relaxation of Supercoiled DNA by DNA Modifying Agents: Detection by Gel Electrophoresis.- The MER Phenotype: Human Tumor Cell Strains Defective in Repair of Alkylation Damage.- Growth-Dependent and Age-Related Changes in the Free Amino Acid Pool of Human Diploid Fibroblasts.- DNA Fragmentation and Sister Chromatid Exchanges Induced by Commercial Auramine O, Purified Auramine, and Michler’s Ketone.- An Attempt to Determine the Origin of DNA Single-Strand Breaks Observed after Treatment of Mammalian Cells with Alkylating Agents.- Localization of Genes Involved in DNA Repair on Human Chromosomes by Using Cell Fusion.- In Vitro Studies on Chemical Carcinogenesis in Balb/c 3T3 Cells.- The Chemical Hazard of Anto-Implantation Assessed and Analyzed Both In Vitro and In Vivo.- Cellular Specificity in DNA Damage, Repair, and Replication during Chronic Carcinogen Exposure.- The Problem of Specificity in the Assessment of Risk from Chemicals and Radiation-Breast Cancer Models.- Author index.