Busby defends Second Event theory

Busby's reply
Letter to the Editor
Commentary on the Second Event Theory of Busby by
(International Journal of Radiation Biology
IJRB 2000, Vol 76, No 1, 119-125)

The publication of this paper is welcome since it raises the question of the plausibility of an idea which may explain a number of epidemiological findings of excess cancer risk following exposure to internal man-made radionuclides.

In its mathematical approach the paper adds little to the calculations I have made (Busby 1998a)and the enhancement factor (EF) for 1 mSv exposure to internal 90Sr differs from that I obtained by a factor of about twenty. This can be explained mainly by the authors' use of a mathematically derived cell-packing fraction which ignores interstitial cell volumes and gave them ten times more cells per unit volume than the number we used which was from biological cell counting using the adult rat (Enesco and Leblond 1962). There is also the statistical factor of 2, which I overlooked. If I revise the second-event enhancement for 90Sr--90Y to allow for this, I obtain an EF of 15 times for exposure at 1 mSv. This EF increases rapidly as the dose decreases and for a dose of 0.001 mGy becomes 4700 for the 90Sr-- 90Y example used. It is ethically unacceptable to argue that second- event genetic damage from man-made pollutants is acceptable just because natural background exposure contributes half of the total number of such incidents at some arbitrary reference exposure level. This is to argue that I may hit my neighbour with a piece of wood (a crime) if he has already suffered from a tree falling on him as a result of a gale (an act of God). By the authors' own calculation, as far as the individual cell is concerned, the existence within it of one atom of Sr has the equivalent effect of doubling the whole external natural background exposure to the person in which the cell resides.

Furthermore, since the ratio of probabilities (external/internal) is a power function of the volume of the element being considered as the site of the effect, it is also possible to pinpoint the site to the chromosome instead of the whole cell, therefore reducing the size of the site and dramatically increasing the enhancement factor. This is due to the breakdown of the concept of dose (i.e. joules/kg) for microscopic volumes.

Edwards and Cox's analysis focuses on 90Sr. Other man-made second event hazards exist which carry much higher enhancements because of more precisely targeted fractionation regimes. Isotopes with shorter daughter half-lives such as 132Te/132I represent a greater hazard with this model. Indeed, the hot particle second-event route clearly has a much greater enhancement factor than any derived from sequential isotope decay. Sub-micron sized hot particles exist with activity designed to cause exact 10 hour lagged sequential damage to cells. The environmentally important 1 micron diameter plutonium oxide particles described by Wilkins et al. (1996) deliver sequential doses to tissue within their alpha decay range that will intercept critical windows in the second-event sequence. It is easy to show that the 0.1 micron range 239Pu particles will deliver a sequence of decays with about the right fractionation to set up and knock down the cell repair replication process. Hot particles of this type are found in estuarine silts in the Irish Sea (Hamilton 1998) and plutonium from Sellafield has been found in humans considerable distances from the Irish Sea coast due to sea-to land transfer (Popplewell 1986). Medical X-raying with a 10-hour interval is another important example of a second event. Any analyis of the plausibility of second event hazards should include such possibilities.

The authors make an interesting point about DDREF and the quadratic dose response that would be expected if second-event processes were the dominant risk at low dose rate. Their reasoning is erroneous for the following reason. The basis of the second-event theory is that a sub-lethal first hit may set up an irreversible cell repair and replication sequence during which the cell is much more sensitive to a second hit and therefore that sequentially correlated hits may carry enhanced risk. The radiation sensitivity of cells in replication is well known: it is the basis of cancer radiotherapy. But a small proportion of cells are always naturally in the sensitive repair replication phase. This proportion is higher for cells with a high natural replication frequency, and these are also the cells which are most sensitive to carcinogenesis (Bergonie and Tribondeau 1906). For the cell fraction naturally in the repair/replication phase, a single hit is equivalent to the second event, since it intercepts the critical window. For this reason, the low dose-response curve would be expected to be complex and generally biphasic since more than one sub-class of cells (replicating and non-replicating) are involved (Busby 1998b). Biphasic responses to low- dose radiation have been reported (Burlakova et al. 1998) and biphasic responses are commonly found in radiation dose response data, though either straight lines are drawn through the points or the complexity of the dose relation is used to deny the radiogenic origin of the effect (Busby and Cato, 1998). Finally, whilst these mathematical models are interesting, I feel that this issue can only be addressed adequately by experiment. The authors have not referred to the considerable evidence that 90Sr carries high risk of genetic damage (Busby 1995). The results of Luning et al. (1963) showing genetic damage in the offspring of mice injected with 90Sr have never been explained. There is also recent evidence that second-event effects are the major contributor to risk in the case of alpha irradiation. Miller et al. (1999) have shown that the measured oncogenicity from exactly one alpha particle hit per cell was significantly lower than for a Poisson distributed mean of one alpha particle hit per cell, which the authors argue implies that cells traversed by multiple alpha particles contribute most of the risk. It is unacceptable that those who are entrusted with protecting the public against hazards from man-made radiation should seek to diminish the dangers from nuclear industry pollutants using facile mathematical models of complex biological systems. It is particularly inappropriate to invoke Bradford Hill's canon against my attempt to resolve a real measurable radiation risk anomaly when the model NRPB use to assess risk from internal isotopes is based on the acute, external, high-dose flash exposure experienced by the Hiroshima bomb survivors.


Bergonie J, and Tribondeau L., 1906, De quelques resultats de la Radiotherapie, et esaie de fixation d'une technique rationelle. Comptes Rendu des Seances de l'Academie des Sciences, 143, 983-985.

Burlakova, E. B., Goloshchapov, A. N., Gorbunova, N. V., Zhizhina, G. p., Kozachenko, A. I., Korman, D, B., Konradov, A. A., Molochkina, E. M., Nagler, L. G., Ozewra, I. B., Rozhdestvenskii, L. M., Shevchenko, V. A., Skalatskaya, S. I., Smotraeva, M. A., Tarasenko, O. M. and Treshchenkova, Yu. A., 1996, Mechanisms of biological action of low dose irradiation. In Consequences of the Chernobyl Catastrophe for Human Health, edited by E. B. Burlakova, (Moscow: Centre for Russian Environmental Policy), pp. 117-146. and see this

Busby, C. C., 1995, Wings of Death: Nuclear Pollution and Human Health. (Aberystwyth: Green Audit).

Busby, C. C., 1998a, Recalculating the Second Event Error. http://www.llrc.org/secevnew.htm

Busby, C. C., 1998b, Averaging errors in the perception of health risks from internal radioisotopes with specific emphasis on mutagenic enhancement due to 2nd event effects from sequentially decaying man-made fission-product beta emitters. In Proceedings of the European Parliament STOA Workshop (February 1998), edited by R. Bramhall (Aberystwyth: Green Audit), pp. 35-50.

Busby, C. C. and Cato, M. S., 1998, Cancer in the offspring of radiation workers: exposure to internal radioisotopes may be responsible. British Medical Journal. 316, 1672-1673.

Enesco, M. and Leblond, C. P., 1962, Increase in cell number as a factor in the growth of the young male rat. Journal of Embryology and Experimental Morphology. 10, 530-562.

Hamilton, E. I., 1998, Marine environmental radioactivity - the missing science? Marine Protection Bulletin, 36(1), 8- 18.

Luning, K. G., Frolen, H., Nelson, A. and Roennbaek, C., 1963, Genetic effects of strontium-90 injected into male mice. Nature, 197, 304-305.

Miller R.C, Randers-Pehrson G, Geard C. R, Hall E. J, Brenner D. J, 1999: The oncogenic transforming potential of the passage of single alpha particles through mammalian cell nuclei, Proceedings of National Academy of Sciences USA 96, 19-22.

Popplewell, D. S., 1986, Plutonium in autopsy tissues in Great Britain. Radiological Protection Bulletin. No. 74 (Chilton: NRPB), pp. 10-12.

Wilkins, B. T., Paul, M. and Nisbet, A. F., 1996, Speciation and Foodchain availability of plutonium accidentally released from nuclear weapons. NRPB R-281 (Chilton: NRPB).

Correspondence to:
Chris Busby, Glyndale, Trinity Road, Aberystwyth, Ceredigion, Wales SY23 1LU, UK.
email: christo@greenaudit.org
Edwards' and Cox's Commentary printed in the same issue of IJRB is reproduced on this site.
Their reply to Busby's letter (above) was printed in the same issue of IJRB and is reproduced on this site.

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