Comments on the article 'Defining hormesis', by EJ Calabrese and LA Baldwin.

In view of the diversity of biological responses and the extent to which many of them remain poorly elucidated, there is merit in the suggestion by Calabrese and Baldwin that the term 'hormesis' should be applicable to those adaptive responses that are characterized by biphasic dose-response relationships, without reference to any associated beneficial or harmful effects. Whether the dose-response relationships for radiation-induced mutations and chromosome aberrations are biphasic in nature is an important question that remains to be resolved.

Radiation hormesis: data and interpretations.

Although the biological effects of large doses of ionizing radiation are predominantly harmful, low-to-intermediate doses have been observed to enhance growth and survival, augment the immune response, and increase resistance to the mutagenic and clastogenic effects of further irradiation in plants, bacteria, insects, and mammals. The existence of these stimulatory, or "adaptive", responses implies that the dose-response relationships for genetic and carcinogenic effects of radiation may be similarly biphasic, or hormetic, in nature, a possibility with far-reaching implications for radiation protection. As yet, however, the extent to which such responses may actually reduce the risks attributable to low-level irradiation remains to be determined, pending further elucidation of the relevant dose-response relationships and the apparent lack of responsiveness in some individuals. Therefore, further research is needed to resolve this question.

Benefits versus risks from mammography: a critical reassessment.

BACKGROUND: The use of mammography has increased rapidly over the last decade. The justification for mammographic examinations is the potential benefit they provide in detecting breast cancer at an early stage and reducing mortality. However, this benefit must be balanced against the associated potential risk of radiation carcinogenesis, economic costs, and a number of other factors. Most publications to date have used radiation risk factors and data from studies that were published over a decade ago, which now have been superseded by the results of more recent epidemiological studies. METHODS: This report examines the current literature regarding the benefits of cancer detection and the risk of radiation carcinogenesis, and calculates the ratio of benefit and risk for women who begin annual mammography screening at different ages. We have used current data to calculate the expected individual benefits and radiation risks associated with annual mammographic screening. RESULTS: It now appears that there is little risk of breast cancer associated with radiation exposure from annual mammography in women over the age of 35, although there is some indication that exposure of younger women may pose a risk for those women in a genetically sensitive subgroup. CONCLUSIONS: New data document that for a woman beginning annual mammographic screening at age 50 and continuing until age 75, the benefit exceeds the radiation risk by a factor of almost 100. Even for a woman who begins annual screening at age 35 and continues until age 75, the benefit of reduced mortality is projected to exceed the radiation risk by factor of more than 25.

Lifespan and autopsy findings in the first-generation offspring of X-irradiated male mice.

Male mice of the C3Hf strain were exposed to 600 R of acute X-rays and, along with unirradiated control males, mated with 101-strain females. The offspring of the treated males were all conceived more than 7 weeks after irradiation, thereby ensuring that they were derived from germ cells exposed as stem-cell spermatogonia. After weaning, the offspring were caged individually and allowed to live their normal lifespan. Tumors and other major pathological disorders were recorded at a careful post-mortem examination. The lesions encountered were typical of those characteristically seen in aging (101 x C3Hf)F1 mice. The results showed no significant differences in lifespan between experimentals and controls. This held true when allowance was made for littermate correlations and for other factors that might contribute to differences among litters. Likewise, there were no significant differences between experimentals and controls in the frequency, severity, or age distribution of neoplasms and other diseases.

Radiation, diagnosis, and management.

The biomedical effects of ionizing and nonionizing radiations include responses that are known to have thresholds ("nonstochastic" effects) as well as responses that are presumed to have no thresholds ("stochastic" effects). The latter include mutagenic, carcinogenic, and teratogenic effects. Present radiation risk management strategies seek to protect completely against nonstochastic effects by preventing anyone from accumulating a dose of radiation in excess of the relevant threshold. Protection against stochastic effects, on the other hand, is sought by limiting the level of radiation exposure sufficiently to keep the resulting risks of such effects within acceptable bounds. For this purpose, a limit is placed on the cumulative dose that may be received by any tissue of the body.

Environmental medicine: introduction and overview.

Human health and longevity have long been known to depend on a complex interplay between hereditary and nonhereditary determinants. The latter include various lifestyle factors, as well as physical and chemical agents encountered in air, food, water, consumer products, the workplace, and the environment at large. Knowledge of these determinants is becoming increasingly important to the physician and other members of society in the maintenance of human health and in the diagnosis and treatment of the diseases of modern life.

Carcinogenic risk assessment in proper perspective.

The evidence that human cancers result in large measure from factors related to life style, working conditions, or other extrinsic variables--and are thus, in principle, preventable (Doll and Peto, 1981)--and the hypothesis that there is no threshold for the carcinogenic effects of many cancer-causing agents (Office of Science and Technology Policy, 1985) have spurred efforts to minimize human exposure to carcinogens. In pursuit of this goal, attempts have been made to identify airborne and other extrinsic carcinogens and to assess the extent to which they contribute to the occurrence of cancer. The status of such endeavors is summarized in the following, without any attempt at a comprehensive review, which would be beyond the scope of this report.

Evolving perspectives on the concept of dose in radiobiology and radiation protection.

Since the discovery of the x ray more than 90 y ago, the biological effects of radiation have been a subject of intensive and continuing study. At the outset, such study was severely hampered by the lack of a suitable method of dosimetry. More than a quarter of a century elapsed before the introduction of a quantitative system for measuring exposure, and another quarter of a century elapsed before the introduction of quantitative units of absorbed dose. In the meantime, the effects of a given dose had long since been found to depend on its distribution in space and time; that is, on the precise spatial and temporal patterns of energy deposition within absorbing tissues and cells. Study of the biological effects of radiation thus led to elaboration of the concept of dose, to take into account relevant microdosimetric parameters. Advances in ongoing research on the molecular mechanisms of radiation effects can be expected to result in further evolution of such coNcepts.