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Biomedical subjects

K H Chadwick

Publications and source records attributed to K H Chadwick.

At least 19 recordsLinked to original sources
PubMed2005

Radiation risk is linear with dose at low doses.

This paper presents a brief argument, based on a mechanistic approach, to show that radiation risk is linear with radiation dose from zero dose up. Similarities in cellular effects lead to the assumption of a common mechanism and the DNA double strand break is identified as the crucial radiation-induced lesion. A cancer model extends the cellular effects to the main radiation risk providing confirmation of the dose effect for cancer at low doses.

DNA↗
PubMed2003

A contribution to the linear no-threshold discussion.

The paper approaches the linear no-threshold (LNT) hypothesis, currently used as the basis for recommendations in radiological protection, from the point of view of the radiation mechanism. All considerations of the validity of the LNT hypothesis based on experiment or epidemiology are dismissed because of the impossibility of deriving statistically significant data at very low doses. Instead, the LNT hypothesis is assessed from a consideration of the mechanism of radiation action. The DNA double-strand break is proposed to be the crucial radiation-induced molecular lesion. A trace is made using a series of correlations that link the DNA double-strand break to effects at the cellular level and these cellular effects are linked to the induction of cancer. Multistep modelling of carcinogenesis is used to take the link through to a consideration of radiation risk. It is concluded that, from the point of view of radiation mechanism, at very low doses the LNT hypothesis of radiation action is valid, that is, the risk function has a positive slope from zero dose.

Cell Death↗
PubMed2002

What can we say about the dose-effect relationship at very low dose?

This paper uses a few sets of low-dose experimental radiobiological data to examine just what these data sets say with respect to the shape of the dose-effect relationship at very low doses. The examination of the data leads to the conclusion that neither experimental nor epidemiological data will ever be statistically strong enough to resolve the debate unambiguously. An alternative approach to the low-dose problem is proposed based on gaining a deeper understanding of both the mechanism of action of radiation and the cellular changes which lead to malignancy. Research spending needs to be directed to more basic investigations of radiation action and to ways by which the information from these studies can be applied to the interpretation of epidemiological data.

Animals↗
PubMed2002

Implications of the analysis of epidemiological data using a two-mutation carcinogenesis model for radiation risks.

A two-mutation carcinogenesis (TMC) model is used as a bridge between cellular radiation biological effects and the incidence of cancer. This model has been applied to several sets of experimental animal and epidemiological data. In this paper the advantage of the model and the implications for radiation risks at low doses are discussed with respect to the age and dose dependence of cancer incidence and the effect of age at exposure on radiation risk; the link between the radiation effect and background cancer incidence and the transfer of radiation risk across different population groups; the implications of acute and protracted radiation exposures for risks at low doses and the dose-effect relationship for radium induced bone cancer.

Age Factors↗
PubMed2001

Bone cancer risk.

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Bone Neoplasms↗
PubMed2000

Analysis of thyroid cancer data from the Ukraine after 'Chernobyl' using a two-mutation carcinogenesis model.

The thyroid cancer data of children in the northern regions of the Ukraine after the reactor accident at Chernobyl were combined with thyroid dose measurements in the same regions and analysed using a two-mutation carcinogenesis model. The best fit was obtained for radiation acting as an initiating agent, i.e. on the first mutation of the model. The observed relatively high increase of thyroid cancer incidence after 1990 in children exposed to radiation released after the reactor accident could be ascribed to the high thyroid doses and the relatively low background thyroid cancer incidence in children. The maximum annual incidence is predicted to occur fairly soon after the reactor accident, i.e. about 10 years. For adults, the predicted relative increase of annual thyroid cancers is much lower than for children younger than 20 years. The modelling results are used to derive risk estimates for radiation-induced thyroid cancer. These risk estimates are dependent on age at exposure, follow-up time and the background thyroid cancer incidence. The calculated excess absolute risk for a population of all ages is about one-third of that currently used by ICRP, but for children the calculated absolute risks are about a factor of 3 higher than derived in other epidemiological studies. The model results indicate that the excess absolute radiation risk per unit dose for children is about the same as or a little lower than that for adults.

Adolescent↗
PubMed1998

Radiation induced chromosome aberrations: some biophysical considerations.

The implications of recent results using FISH chromosome painting and soft X-ray exposures for the mechanisms of chromosome aberration formation are discussed. It is concluded that the evidence in favour of exchange aberrations arising from one radiation induced chromosome break has increased to the point where a 'change in paradigm' from the older breakage-reunion hypothesis needs to be taken seriously into account. A potential role for recombinational repair of DNA double strand breaks, as known in yeast, in the formation of aberrations in mammalian cells is presented and the relationship between DNA repair studies and radiation cytology is emphasized.

Animals↗
PubMed1998

Health consequences of Chernobyl and other radiation accidents. Report on the European Union Cluster Contractors' workshop (San Miniato, Italy, 17-22 June 1997).

The Radiation Protection Research Unit of the European Commission has been supporting collaborative research projects on the radiological consequences of the Chernobyl accident since 1991. However, in the Fourth Framework Programme of the Commission which started in 1996, the collaboration with scientists in the former Soviet Union has been placed on a different footing, and the programme has been expanded to include other regions, especially in Russia and Kazakhstan, where previous nuclear incidents have led to the exposure of workers and the local populations and to widespread radioactive contamination. There are 15 projects on health-related studies in the newly started programme, and in order to improve the collaboration between the different scientists working in these projects a Cluster Contractors' Meeting was organised in San Miniato, Italy, in June 1997 with the participation of some 50 scientists from the European Union (EU) and the Newly Independent States (NIS). This report summarizes the different topics, including molecular biology and treatment of childhood thyroid cancer, various epidemiological studies and dose reconstruction, which were discussed at the meeting and which form the major projects in the new collaborative programme.

Chromosome Aberrations↗
PubMed1997

Multistage carcinogenesis modeling and the initiation event.

Carcinogenesis is generally considered to be a multistage process classified under "initiation," "promotion," and "progression," and it is therefore of interest to know how radiation might affect them. Models which are currently being used with some success to analyze a variety of data are based on the two-mutation with clonal expansion model developed by Moolgavkar and Knudson [J Natl Cancer Inst 66:1037-1052, 1981]. These models imply that the "initiation" event would be a mutation but also imply that "progression" also involves mutation and that both these events could be influenced by radiation. The models offer the possibility of calculating the incidence of cancer over lifetime and can simultaneously provide the age and dose dependence of cancer. The models have implications for radiation protection and imply that radiation risk is related to spontaneous cancer incidence and that spontaneously induced "initiation" may also be associated with radiation-induced cancer.

Age Factors↗