Radiation Carcinogenesis and DNA Alterations

This volume is based on the proceedings of an Advanced Study Institute (ASI) sponsored by the North Atlantic Treaty Organization (NATO) held October 1984 in Corfu, Greece. The meeting received finan­ cial support from the United States Department of Energy and the United States National Cancer Institute. A plethora of recent developments in the molecular biology of DNA are leading to new ideas concerning how DNA alterations might be involved in the mechanism of radiation carcinogenesis. Evidence is accumulating that genetic sequences, known as oncogenes, are involved in the translation of DNA molecular alterations into phenotypic changes associated with malignant cells. For example, a chromosome break often occurs at or near the loca­ tion of a specific oncogene in Burkitt's lymphoma. Such breaks could represent initial lesions in a translocation process that activates the oncogene by inserting it at a new location, eg., near an active pro­ moter. Since breakage of the DNA is one of the principal ways that ion­ izing radiation affects mammalian cells, these new molecular ideas sug­ gest ways that radiation-induced DNA breaks might be involved as initial events in carcinogenesis. While the possible involvement of oncogenes in radiation carcino­ genesis is an exciting new development, a direct sequential connection between early molecular changes in DNA and later tumor development has yet to be established. Accordingly, there is a tremendous need for experimental studies of how DNA alterations might convert normal cells to cancer cells.

Inhalt

Carcinogenesis in Humans and Animals.- 1. Follow-up Studies of Patients Treated by X-ray Epilation for Tinea Capitis.- 2. Tumour Induction in Experimental Animals after Neutron and X-irradiation.- 3. Dose-Response for Radiation-Induced Cancer in Rat Skin.- 4. Experimental Radiation Carcinogenesis.- 5. Radiation Carcinogenesis and the Hair Follicle.- 6. Dose-Incidence Relations for Radiation Carcinogenesis with Particular Reference to the Effects of High-LET Radiation.- 7. Assessment of the Lung Cancer Risk from Radiation Exposures Due to Air tightening of Dwellings for Energy Conservation.- 8. Carcinogenic Effects of Inhaled Radionuclides.- Transformation In Vitro.- 9. Mechanisms of Radiation Transformation.- 10. The Radiobiology of In Vitro Neoplastic Transformation.- 11. Induction of Chromosome Aberrations and Malignant Transformation in Different Cell Lines by Photons and Monoenergetic Neutrons.- 12. Radiation Induced Transformation in Primary Differentiated Thyroid Cultures.- Ultraviolet Radiation.- 13. The Induction and Repair of Ultraviolet Light Damage in Mammalian Cells.- 14. Alterations in Benzo(a)pyrene Metabolism and its DNA Adduct Formation in Skin of Mice Chronicallly Exposed to Ultraviolet-B Radiation.- 15. Immunosuppression by Ultraviolet Radiation; Possible Role of Cis-urocanic Acid, a Product of UV Irradiation.- DNA Strand Breaks and Chromosome Alterations.- 16. DNA Damage and Chromosome Aberrations.- 17. Chromosome Break-points, Somatic Mutation and Oncogene Activation: Some Comments.- 18. The Yield of Chromosomal Aberrations and its Correlation with Other Biological Endpoints.- 19. X-ray-Induced DNA Double Strand Breaks in Polynucleosomes.- 20. Chemical Inhibition of the Repair of DNA Single Strand Breaks Produced by X- irradiation or Hydrogen Peroxide in Cultured Mammalian Cells.- 21. Conjugated Dienes and TBA Reactive Material as Components of Chromosome Breakage Factors.- 22. Conversion of Covalently Closed Circular DNA into Circular and Linear DNA by Ionizing Radiation in the Presence and Absence of DNA-binding or Intercalating Drugs.- 23 How Soon After Irradiation Do Chromosome Aberrations Form and Become Irreversible: A Direct Analysis by Means of the Premature Chromosome Condensation Technique.- 24. Production by Radiation of DNA Double Strand Breaks in Three Mammalian Cell Lines and Their Repair in Fetal Human Fibroblasts.- Mutations and Gene Expression.- 25. The Role of Oncogenes in Multistage Carcinogenesis.- 26. A Regulatory Sequence of Simian Virus 40 Is Inactivated by UV-Induced Damage.- 27. Mechanisms of Spontaneous Mutagenesis: Implications for Spontaneous Carcinogenesis.- 28. A Method for the Detection of Neo-antigens in X-ray Induced Thymomas of C57B1/ 6 Mouse.- 29. Visible Light Induced Killing and Mutation of Acriflavine Sensitized Chinese Hamster Cells.- 30. Oncogenes Activated in Radiation-Induced Rat Skin Tumors.- 31. Mutagenesis in Mammalian Germ Cells by Radiation or Nitrogen Mustard-A Comparative Study.- 32. Gene Amplification in Mammalian Cells After Exposure to Ionizing Radiation and UV.- 33. Regulation of Gene Expression at the Translational Level in Plant Embryo.- Molecular Alterations In DNA.- 34. Prooxidant States and Promotion.- 35. Molecular Aspects of DNA Damage and its Modification.- 36. 5-Hydroxymethyl Uracil: A Product of Ionizing Radiation and Tritium Transmutation Formed in DNA.- 37. Characterization of Two CHO Variants in Respect to MNNG-Induced Cell Killing, Mutations, and Repair of Methylated DNA Bases.- 38. Investigation of the Sensitivity of Oriented ? X-174 DNA to Ionizing Radiation.- 39. Radiosensitizers and Thymine Base Damage.- Repair of Dna Alterations.- 40. Human Cancer-Prone Disorders, Abnormal Carcinogen Response and Defective DNA Metabolism.- 41. New DNA Repair Systems and New Insights on Old Systems in Escherichia Coli.- 42. The Relationship of Defective Recognition of DNA Damage to Cancer in Ataxia-telangiectasia.- 43. Multifunctional Repair Enzymes Excise Thymine and Adenine Residues Damaged by Ionizing Radiation from DNA.- 44. Age and Species Specific Variation in DNA Excision Repair in Cultured Skin Fibroblasts.- Non-Stochastic and Cell Cycle Effects.- 45. Non-stochastic Effects: Compatibility with Present ICRP Recommendations.- 46. Carcinogenic Potential of Incinerated Low-level Radioactive Waste: Cytopathologic Evaluation.- 47. Carcinogenic Potential of Incinerated Low-level Radioactive Waste: Electrophoretic Resolution.- 48. X-ray Low Dose Relationships Within the G2 Phase of Chinese Hamster Cells.- Models of Radiation Carcinogenesis.- 49. The Dependence of Dose-Effect Relations for Various Responses in Mammalian Cells on Radiation Quality, Implications for Mechanisms of Carcinogenesis.- 50. The Physics of Absorbed Dose and Linear Energy Transfer.- Author Index.