Evidence from Animal Experiments

Life Span Data

In contrast to experiments showing that radiation shortens the life span, some early publications reported apparent radiation-induced life lengthening following exposure to low levels of single or protracted doses of radiation (Lorenz 1950; Lorenz and others 1954). Statistical analyses of the distribution of deaths in these studies indicate control animals usually show a greater variance around the mean survival time than groups exposed to low doses of radiation. In addition, the longer-living irradiated animals generally have a reduced rate of intercurrent mortality from nonspecific and infectious diseases during their early adult life, followed by a greater mortality rate later in life. Since these investigations were conducted under conditions in which infectious diseases made a significant contribution to overall mortality, the interpretation of these studies with respect to radiation-induced cancer or other chronic diseases in human populations must be viewed with caution.

Problems with variability in controls was a major difficulty in the early studies before animal maintenance and heath care issues were dealt with by transitioning to the use of specific pathogen-free (SPF) facilities; this change to SPF facilities substantially reduced interexperimental variability. For example, the cited data of Lorenz (1950) show a small difference in life span in mice exposed to 0.11 r/d compared to controls; the irradiated group lived somewhat longer than the unirradiated group, but the difference was not significant. A French study (Caratero and others 1998) shows life lengthening in irradiated mice compared to controls; unfortunately, the control life spans were significantly shorter by 100–150 d than any in other published data for this mouse strain (Sacher 1955; Congdon 1987).

Tumor Incidence Data

Two studies have reported a significant reduction in tumor incidence of lymphoma in animals that have a high spontaneous tumor incidence (>40%; Covelli and others 1989; Ishii and others 1996). A paper by Ishii and colleagues (1996) describes a reduction in lymphoma incidence after chronic, fractionated, low-dose total-body irradiation of AKR mice with a spontaneous lymphoma incidence of 80.5%. The spontaneous lymphoma incidence was decreased significantly (to 48.6%) by 150 mGy X-irradiation delivered twice a week for 40 weeks. A protocol of 50 mGy three times a week gave a smaller (not statistically significant) decrease to 67.5% lymphoma incidence. The mean survival time was significantly prolonged from 283 d for the control animals to 309 d with the three-exposure-per-week protocol and to 316 d with the twice-a-week protocol.

In a study by Covelli and colleagues (1989), a decrease in incidence of malignant lymphoma at low doses of radiation (46 and 52% age-adjusted incidence at X-ray exposures of 500 and 1000 mGy versus 57% incidence in control animals) shows a reduction in tumor incidence relative to the control frequency. After peaking at 60% lymphoma incidence (3000 mGy), the frequencies decline, “possibly due to cell inactivation becoming predominant at higher doses over the initial transforming events.”

The reduction in spontaneous tumors noted in the previous two studies may in some way be related to the high spontaneous lymphoma incidence in this mouse strain. In the Ishii study, the authors speculate that possible mechanisms may include augmentation of the immune system or initiation of an “adaptive response.” One might also consider that the substantial doses delivered to the animals in this study (6000 and 12,000 mGy) are effectively acting as radiotherapy in the reduction of spontaneous tumor incidence. Human populations, which have a wider spectrum of “spontaneous” tumors occurring at a lower incidence, may not be expected to respond to radiation in the same way as mouse strains with high lymphoma incidence.

HORMESIS AND EPIDEMIOLOGY

The term hormesis is not commonly used in the epidemiologic literature. Rather, epidemiologists discuss associations between exposure and disease. A positive association is one in which the rate of disease is higher among a group exposed to some substance or condition than among those not exposed, and a negative (or inverse) association is one in which the rate of disease is lower among the exposed group. If an association is judged to be causal, a positive association may be termed a causal effect and a negative association could be termed a protective effect.

One type of epidemiologic study that has been used to evaluate the association between exposure to radiation and disease is the “ecologic” study in which data on populations, rather than data on individuals, are compared. These data have been used to argue for the existence of radiation hormesis.

Another example of an ecologic study is the evaluation of geographic areas with high background levels of radiation compared to areas with “normal” background levels. The fact that cancer rates in these high-background-radiation geographic regions are not elevated is sometimes cited as evidence against a linear no-threshold model (Jaworowowski 1995).

It is also true that certain populations residing in high-background areas, such as occur at high altitudes, have lower levels of health problems than those residing at lower altitudes. This observation has been interpreted by some as evidence for a hormetic effect of radiation. BEIR V discussed



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