The origins of the multinucleated osteoclast have been controversial, with osteogenic precursors and haematopoietic stem cells as candidates. Recent evidence for the latter is persuasive but circumstantial. We report here direct evidence obtained in radiation chimaeras from a natural cytoplasmic cell marker transmitted by the donated haematopoietic stem cell.

Increasing numbers of young people are now being cured of certain neoplasms by radiotherapy and chemotherapy. Such people will naturally wish to lead a normal life and possibly to have children. Therefore the question of the effect of radiation and cytotoxic drugs on the reproductive capacity of these patients has become important. The purpose of this report is to review the information available on the effect of radiation on fertility in man. Direct information on radiation effects on human fertility is available from reports on therapeutic exposure and deliberate experimental exposure. Although the total number of cases involved is small, a number of general principles emerge. In males, fractionated irradiation of the testes may be more harmful than acute, at least up to total doses of about 600 cGy (rad). Fractionated doses greater than 35 cGy cause aspermia, the time taken for recovery increasing with dose, and after more than 200 cGy aspermia may be permanent. In females, response varies with age as well as dose. For example, 400 cGy may cause a 30% incidence of sterility in young women, but in women aged above 40 years it results in 100% sterility. However, individuals of either sex show a degree of variation in their response to irradiation.

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Isolated rat liver, when perfused with medium containing bovine growth homone produced somatomedin-like activity (liver somatomedin). Liver somatomedin is useful in studies of the hormonal control of the cartilage plate in vitro, since unlike serum it is not contaminated with other hormones or growth factors (apart from growth hormone). Chondrocytes isolated from various regions of the growth cartiage responded differently to liver s-omatomedin; proliferative chondrocytes, like those isolated from the articular cartilage, showed increased [3H]thymidine uptake in response to liver somatomedin, whereas hypertrophic chondrocytes did not respond. It is suggested that there is a reduction in the response to somatomedin by growth plate chondrocytes as they pass from the proliferative to the hypertrophic state. Thyroxine, thought to be involved in thr processes of hypertrophy and new bone formation, did not directly affect [3H]thymidine uptake by proliferative chondrocytes, but inhibited stimulation of both their activity by liver somatomedin. Mesurement of [3H]thymidine uptake by isolated articular chondrocytes may provide a useful assay for both liver and serum somatomedin. The graded response of chondrocytes to increasing concentrations of liver somatomedin paralleled the response to increasing levels of serum somatomedin.

The absorbed dose of low LET radiation that would be lethal (due to bone marrow failure) to 50% of an exposed human population is a matter for concern in planning for the consequences of an accident to a nuclear reactor and in the event of nuclear war. Since accidents with radiation-generating equipment or in the nuclear fuel processing industry might provide relevant human data, published accounts of these are reviewed. Two accidents, one in the USA, the other in Yugoslavia, both involving exposure to neutrons as well as gamma-rays, are identified as possibly satisfying the criteria of uniformity of dose, magnitude of dose and dose rate necessary to provide useful information on the value of LD50/60 for man. The symptomatology of the exposed individuals is discussed in terms of the published doses. Detailed examination of the dosimetry for these two accidents revealed possible ambiguities and a thorough re-examination has been carried out, the results of which are reported in detail in the Appendix. This indicates considerable and largely unresolvable uncertainty in the magnitude of the dose to exposed individuals when expressed as the low LET equivalent dose in bone marrow. It is also shown that the relationship between severity of effects and dose to exposed individuals is not the same for both accidents and it is argued that the experience from the Yugoslavian accident is more relevant to the determination of the sensitivity to radiation of an exposed human population. Given the uncertain nature of the accident data and the small amount of other relevant human data at present available, the uncertainty of current knowledge of man's sensitivity to the acute effects of exposure to ionising radiation is discussed.