Cosmic radiation and cancer mortality

Zusammenfassung Es wird versucht, die Krebssterblichkeit in verschiedenen Orten und Ländern mit der dort vorhandenen Intensität der kosmischen Strahlen in Verbindung zu bringen. Gewisse klinische Faktoren beeinflussen allem Anschein nach die offensichtliche Abhängigkeit der Krebssterblichkeit von der geographischen Breite und damit von der Stärke der kosmischen Strahlen. Im Hinblick auf neuere experimentelle Ergebnisse (Erzeugung von kosmischen Strahlenschauern unter Blei und Krebserkrankungen) wird auf den Zusammenhang zwischen Krebssterblichkeit und «percent urbanity» hingewiesen. Die Häufigkeit bestimmter Krebsarten ist indessen, das muß betont werden, von der geographischen Breite vollkommen unabhängig. Bei der Auswertung des angeführten Materials ist einige Vorsicht notwendig; definitive Schlußfolgerungen sind noch nicht möglich. Es werden Vorschläge zum Ausbau dieser Forschungen gemacht.     

Biochemical aspects of radiation biology

In order to analyze the mechanisms of biological radiation effects, the events after radiation energy absorption in irradiated organisms have to be studied by physico-chemical and biochemical methods. The radiation effects in vitro on biomolecules, especially DNA, are described, as well as their alterations in irradiated cells. Whereas in vitro, in aqueous solution, predominantly OH radicals are effective and lead to damage in single moieties of the DNA, in vivo the direct absorption of radiation energy leads to 'locally multiply-damaged sites', which produce DNA double-strand breaks and locally denatured regions. DNA damage will be repaired in irradiated cells. Error free repair leads to the original nucleotide sequence in the genome by excision or by recombination. "Error prone repair"(mutagenic repair), leads to mutation. However, the biochemistry of these processes, regulated by a number of genes, is poorly understood. In addition, more complex reactions, such as gene amplification and transposition of mobile gene elements, are responsible for mutation or malignant transformation.     

Cell kinetics and radiation pathology

Conclusion Radiation pathology is a general term describing the damage that occurs in tissues after irradiation. After the very low doses, received by the normal working population, no major pathology is seen. There is a hazard of cancer induction if DNA damage that has been inflicted in an individual cell is repaired in such a way that the DNA remains intact but rearranged. This radiation carcinogenesis is however a low risk compared with many chemical carcinogens in the environment and in cancer chemotherapy.The treatment of cancer by radiation is now commonly accepted as one of the most effective forms of treatment. It can kill tumour cells effectively, but the dose that can be given is limited by the normal tissues that are inevitably included in the beam. Cell function is maintained for some time even after very large doses. However normal tissues show a loss of function and structure because the proliferating subcompartment of each tissue is depleted as the radiation injured cells fail to divide and die. The time at which the cell deficit is detected varies from hours in some tissues to months or years in others. It depends upon the normal rate of cell turnover. The apparent sensitivity of each tissue therefore depends upon the time at which the assessment is made. Lung and kidney would appear very resistant at 1–3 months post irradiation, but would seem very radiosensitive at 6–12 months as their latent damage is expressed.The ultimate expression of radiation pathology is the death of the whole animal as the essential organ function fails. The time of this death is only comprehensible if the time sequence and the proliferation kinetics of the target cells are taken into account. It must be recognised that it is initial damage to the clonogenic cells, not to the differentiated cells per se that is important.     

Biochemical aspects of radiation biology

Summary In order to analyze the mechanisms of biological radiation effects, the events after radiation energy absorption in irradiated organisms have to be studied by physico-chemical and biochemical methods. The radiation effects in vitro on biomolecules, especially DNA, are described, as well as their alterations in irradiated cells. Whereas in vitro, in aqueous solution, predominantly OH radicals are effective and lead to damage in single moieties of the DNA, in vivo the direct absorption of radiation energy leads to locally multiply-damaged sites, which produce DNA double-strand breaks and locally denatured regions. DNA damage will be repaired in irradiated cells. Error free repair leads to the original nucleotide sequence in the genome by excision or by recombination. Error prone repair (mutagenic repair), leads to mutation. However, the biochemistry of these processes, regulated by a number of genes, is poorly understood. In addition, more complex reactions, such as gene amplification and transposition of mobile gene elements, are responsible for mutation or malignant transformation.     

Genetical effects of radiation and chemicals

Zusammenfassung Die populären Auffassungen der durch Bestrahlung erzeugten genetischen Schädigungen irren gewöhnlich weit vom Ziele, und zwar in entgegengesetzten Richtungen. Oft hört man die Behauptung, dass bestrahlte Eltern die Gefahr laufen, Missgeburten oder sonstwie anormale Nachkommen zu haben. Noch öfter werden die genetischen Gefahren ionisierender Strahlen als unbeträchtlich und nicht beachtenswert hingestellt. In Wirklichkeit sind diese Gefahren sehr ernst zu nehmen. Sie betreffen aber nicht Individuen, sondern die menschliche Rasse als Ganzes. Über ihre Natur sind wir gut unterrichtet, über ihr Ausmass können wir uns gegenwärtig nur sehr ungenaue Vorstellungen machen. Genetisch unterschwellige Strahlungsdosen gibt es nicht; die gesetzlich festgesetzte Toleranzdosis muss daher einen Kompromiss darstellen zwischen gegenwärtigem Nutzen und zukünftigen Gefahren.     

Increased radiation mortality by lead acetate

Summary The mortality of X-irradiated rats and mice was increased if a nontoxic dose of lead acetate was given i.v. 3 and 7 days following radiation. The increase was equivalent to 100 R for X-ray doses between 790 and 540 R.The basic experiments have been carried out 1967/1968 in the Heiligenberg-Institut.We are indebted to Mr Sunil Chaudhuri and Mr Thomas Beck for their technical assistance.     

Biological effectiveness of solar UV radiation in humans

Solar UVB radiation is prejudicial to the health of humans in a number of ways. Erythema and photodermatoses are acute reactions of the skin; keratitis and conjunctivitis are acute reactions of the eye. Various types of skin cancer, accelerated aging of the skin, and cataract formation in the crystalline lens are reactions that appear with great latency. UV radiation can also cause damage to the immune system and DNA. For the period 1981–1991, an increase in erythemal effective UVB radiation of +(7±4)% per decade was measured in a non-pulluted high mountain area (Jungfraujoch, 3576m a.s.l., Switzerland). This increase is related to a decrease in stratospheric ozone. The effects on human health are discussed. A 10% ozone reduction increases non-melanoma skin cancer by 26% and cataract by 6 to 8%.     

The production of chromosome structural changes by radiation

This paper attempts an update and comment upon some of the topics of chromosome aberration formation which Lea raised in Chapter VI of his classic work 'Actions of Radiations on living Cells'. Only the first nine sections of this chapter are covered, which deal primarily with the qualitative aspects of aberrations, their formation, classification and interrelationships. In commenting upon these topics, pertinent references are made to work with mammalian and human cells. Increased knowledge of the importance of DNA as a fundamental target and the integral part it plays in the complex structure of the chromosome, coupled with cellular techniques not available to these earlier workers necessitate some revision and modification of early ideas. However, inspite of the enormous accumulation of data and ideas since the original work was published in 1946, the foundation that these early workers laid is still very solid. Surprisingly, we are still puzzled by many of the problems that perplexed them.     

Teratogenic interactions between cadmium and radiation in mice

Summary Mouse embryos were exposed to various doses of cadmium and/or X-rays on day 8 of gestation. The combined treatment exerted an antagonistic effect regarding the teratogenic action of the two agents.     

The production of chromosome structural changes by radiation

Summary This paper attempts an update and comment upon some of the topics of chromosome aberration formation which Lea raised in Chapter VI of his classic work Actions of Radiations on Living Cells²⁴. Only the first nine sections of this chapter are covered, which deal primarily with the qualitative aspects of aberrations, their formation, classification and interrelationships. In commenting upon these topics, pertinent references are made to work with mammalian and human cells.Increased knowledge of the importance of DNA as a fundamental target and the integral part it plays in the complex structure of the chromosome, coupled with cellular techniques not available to these earlier workers necessitate some revision and modification of early ideas. However, inspite of the enormous accumulation of data and ideas since the original work was published in 1946, the foundation that these early workers laid is still very solid. Surprisingly, we are still puzzled by many of the problems that perplexed them.