Leukaemogenic effect of repeated inoculations with small doses of Tennant virus in BALB/c mice

article
Dose response studies of oncogenic viruses in animals are usually restricted to single inoculations. The study of the effect of dose fractionation has been a rather neglected subject in this field. An important question is whether the combined effect of the small doses is less than the effect of a single exposure to the same total dose. In this study of dose fractionation of a murine leukemia virus the opposite effect was observed. Mice were injected 3 times/wk. They were examined twice/wk for splenomegaly and/or swollen lymph nodes. The animals were then autopsied and histologically examined for confirmation of the development of leukemia. The survivors were kept under observation only up to the age of 10 mth. After that age, the first spontaneous lymphoreticular neoplasms begin to appear in this strain. The results show that a 1,000 fold dilution is still fully leukemogenic. Higher virus doses or repeated inoculations tend to shorten the latency period. There is no indication that dose fractionation leads to a lower incidence or longer latency. Repeated inoculations with low doses of virus produce a significantly higher leukemia incidence than a single injection with a much higher dose (for instance, 12 x 10-6 instead of 1 x 10-4). A possible explanation is that continuous exposure to even very small numbers of virus particles induces immunologic unresponsiveness to the virus, so that these small numbers may be propagated in the host. Alternatively, autointerference induced by a moderate dose of virus may plan an important part.
TNO Identifier
227712
ISSN
00280836
Source
Nature, 251(5471), pp. 155-156.
Pages
155-156
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