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Biomedical subjects

R H Mole

Publications and source records attributed to R H Mole.

At least 37 records · Page 2Linked to original sources
PubMed1987

Irradiation of the embryo and fetus.

The human evidence on radiation damage to the individual developing in utero is confined to mental impairment and carcinogenesis. New evidence is becoming available about levels of mental impairment of direct interest to radiological protection, but as yet no framework of understanding exists to allow quantitative predictions for the purposes of radiological protection. There is general agreement that malignant disease has been increased following antenatal radiography but no unanimity yet in concluding that irradiation was the main causal factor: reasons are given for accepting that radiography was the cause. Recent increases in biological understanding suggest why maldevelopment is not to be expected after irradiation of the conceptus. A clonal hypothesis for organogenesis provides a reasonable explanation for quantitative aspects of experimental observations on teratogenesis by ionising radiation, including the commonly found highly curvilinear dose-response relationship, the occurrence of so-called critical stages of sensitivity after exposures of a few hundred roentgens, and the reduction in frequency of induced abnormality with protraction of exposure. Clonal hypotheses predict that there will be a virtual threshold for polycystic (non-stochastic) forms of radiation damage. It may be misguided to adopt a linear dose-response relationship for deriving risk estimates for the practical purposes of radiological protection unless some mechanism for production of clinically evident harm can be advanced which provides a plausible reason for expecting linearity.

Animals↗
PubMed1986

Radiation-induced acute myeloid leukemia in the mouse: experimental observations in vivo with implications for hypotheses about the basis of carcinogenesis.

Acute myeloid leukaemia induction by X- and gamma-rays in 4 mouse strains follows the same dose-response aD2e-lambda D. The (dose)2 interaction disappears within 3 days. AML appears earlier when syngeneic marrow cells are injected 3 days after irradiation, minimum latent period and final frequency remaining unchanged. Dose-responses for brief and protracted exposures are quite different for non-myeloid 'leukemia'. The results seem incompatible with a common model for initiation of both leukaemia categories and with orthodox concepts that initiation is a stable state and must be followed by multiple events over a period of time before cells express fully malignant behaviour.

Animals↗
PubMed1984

Sodium in man and the assessment of radiation dose after criticality accidents.

Recent observations on the sodium content of the human body, both total and exchangeable, using isotope dilution methods and activation of sodium by whole-body irradiation with neutrons in the course of clinical research, suggest that ICRP Reference Man is a misleading guide to the sodium content of the body and of the skeleton and its parts. They also show that reasonable predictions of body sodium content can be made from body weight, height and age, or even from body weight alone. Mean sodium in the average man is about 1.04 g per kg and in the average women about 0.98 g per kg in British and N. American populations. Within each sex mean tissue concentration is inversely related to body weight. Review of the dosimetry for the criticality accident at Y-12 Oak Ridge shows that dose estimates should be increased by about 10% because whole blood values of 24Na were relied on instead of plasma values. Taking account of body build reduces the range of dose amongst the four most heavily irradiated subjects. The absorbed doses reported for the subjects exposed at the criticality accident at Vinca, Yugoslavia, need to be increased by about 30% because the normal sodium content of the body was grossly overestimated. The more severe clinical picture at Vinca than at Y-12 is now more easily understood in terms of differences in dose. These changes are solely the result of improved information about sodium in the body. Other uncertainties in the dosimetry at Y-12 and Vinca are unaltered.

Accidents, Occupational↗
PubMed1984

The LD50 for uniform low LET irradiation of man.

Previously published estimates of the whole-body radiation dose expected to kill 50% of a normal human population, the LD50, have rarely been based explicitly on evidence. The difference which might result from medical treatment seems to have been markedly over-valued. The available and relevant evidence about severe haematopoietic damage in man uncomplicated by tissue necrosis is indeed very scanty. It comes from 20 cases of therapeutic whole-body exposure to gamma rays and from two criticality accidents involving nine subjects, one of whom died, and when exposure was to neutrons as well as gamma rays. The observations suggest a judgment that 4.5 Gy (450 rad) absorbed dose in the bone marrow for energetic and therefore penetrating gamma rays giving reasonably uniform irradiation of the marrow could be regarded as the LD50 in circumstances where those irradiated were protected from thermal radiation and blast damage and from neutrons and beta rays. Examination of all the available experimental data on acute lethality following whole-body exposure to low LET radiation shows a remarkably similar co-efficient of variation of the LD50 in five species of large animal. If the same value is adopted for the human species, a quantitative estimate of the human LD50 can be inferred from the human evidence discussed. This reinforces the judgement that it is about 4.5 Gy. The use of observations after criticality accidents is examined in detail in an Appendix. The Vinca accident does not clearly meet the criteria for relevancy but there is no other instance of death in man from an uncomplicated brief whole-body exposure to ionising radiation where the bone-marrow dose can be estimated, and a possible judgment made of the value for the LD50.

Accidents↗
PubMed1983

Myeloid leukaemia frequency after protracted exposure to ionizing radiation: experimental confirmation of the flat dose-response found in ankylosing spondylitis after a single treatment course with X-rays.

The dose-response for leukaemia induction by exposure to ionizing radiation protracted over several weeks was largely independent of dose not only in X-rayed patients with ankylosing spondylitis but also in experimentally gamma-rayed CBA/H mice. In the experiment the induced leukaemia frequency of acute myeloid leukaemia was independent of a several thousand-fold variation in physical dose rate. Any difference in leukaemia induction between brief and protracted exposures must therefore depend on specifically biological consequences of protracted exposures. Experimental analysis is required to provide the guides for inference about risks of low level exposure from observations on relatively heavily irradiated populations.

Animals↗
PubMed1983

The dose-response for x-ray induction of myeloid leukaemia in male CBA/H mice.

The form of the dose-response for induction of malignant diseases in vivo by ionizing radiation is not yet established in spite of its scientific interest and its practical importance. Considerably extended observations have confirmed that the dose-response for acute myeloid leukaemia induced in male CBA/H mice by X-ray exposure is highly curvilinear. The dose-response was well fitted by the expression aD2e-lambda D (D = dose) in agreement with induction at the cellular level in proportion to D2 over the whole dose range 0.25-6.0 Gy. The factor e-lambda D accounts for the inescapable concomitant inactivating action of the inducing irradiation. The quantitative aspects of induction of myeloid leukaemia by ionizing radiation are unlike the induction of genetic mutation or cell inactivation and suggest that interaction of two adjoining cells is an essential element in radiation leukaemogenesis.

Animals↗
PubMed1982

Radiation-induced myeloid leukaemia in CBA/H mice: a non-immunogenic malignant disease in syngeneic mice.

In vivo growth characteristics of myeloid leukaemia induced by whole-body irradiation of CBA/H male mice were examined in the strain of origin by procedures expected to enhance or depress immunological responses. Syngeneic growth in vivo (survival time and frequency of takes) was not modified by attempted active immunization with radiation-inactivated cells or by sublethal whole-body irradiation of recipients before inoculation of small numbers of clonogenic cells. Since the growth stimuli involved in in vivo repair of severely damaged normal haemopoietic tissue also did not modify the growth of the radiation-induced leukaemia cells in syngeneic passage, their growth in vivo in the irradiated primary hosts can be regarded as autonomous by the stage at which leukaemia was diagnosed. Challenge inocula in the "immunization" experiments were 1-9 clonogenic cells from 4 different passaged lines and in the whole-body radiation experiments, 1-10(3) clonogenic cells derived from 11 different primary hosts and 4 different passaged lines.

Animals↗
PubMed1982

Reflections on the terms stochastic and non-stochastic as currently used in radiological protection.

The meanings, past and present, of the word stochastic are discussed and related to the way in which "stochastic" and "non-stochastic" may be used to describe the categories of biological damage from ionizing radiation. "Haplocytic" and "polycytic" are suggested as alternatives: these terms allow a classification according to the numbers of cells involved initially and, therefore, according to the basic mechanisms. For more speculative concepts relating to carcinogenesis the word "syncytic" is suggested, together with some potentially useful terms derived from it.

Probability↗