Dose and Biological indicators one or both of these genes permits one to say that the patient has a definitely increased probability of developing the disease. or already has it. Similar findings may become available with respect to other malignancies. e.g.. breast cancer in women. Although it is beyond the scope of this paper to deal with the progress that is being madein this area (see other papersin this symposium). the approach of course has the potential of completely altering the situation with respect to being able to provide an individual-specific (1.e.. medical) severity of effect diagnostic and prognostic probability. Anaddedproblem exists with respect to the Causative agent. be it radiation or otherwise. With cancers and radiation. the criterion for radiation causation has been the appearanceofthe disease, €.g.,a given form of cancer, in excess numbers among the atomic bomb survivors. Whatcriteria for an agent being causative or contributory is to be used in general for diseases other than can- a wher 8 cer and agents other than radiation? As noted above, markers such as chromosomal abnormalities have been used to give someindication of the dose of radiation received by individuals. and in the population. However. there has been little correlation between the type and-number of chromosomal aberrations tn any given individual. and the probability of that individual developing cancer. In the context of the atomic bombsurvivors, both the incidence of radiation attributable cancers and persistent chromosomalchanges such as reciprocal translocations have been studied (T. Strawme, personal communication). In Figure 7 is shown a plot of both the excess incidence of reciprocal translocations in bone marrowcells and the incidence of leukemia. as a function of the estimated DS86 dose. One can seethat. although the relationshipis initially curvilinear. the chromosomal aberration incidence tracks very closely the estimated dose. Thus. as expected (Fig. 8). the incidence of cancer (shown for solid tumors only). is a linear function of the “severity of effect” as indicated by the numberof reciprocal translocations. This approach is useful, because it does have the advantages noted above in connection with Su;z24a| | é , ' Excess leukemia cases/10,000 PY of which one maybe inherited. Thus. finding 0.3 Fraction cells with aberrations associated diseases. A notable exceptionis retinoblastoma. which requires two gene changes Relationship between incidence of aberrations and leukemia (both cities combined) t . / Aberrations DS&6 dose. Gy Fig. 7. Plot showing howwell both the fraction of cells with chromosomal aberrations and the excess leukemia incidence track the dose to the atomic bomb survivors. particularly in the dose region up to about 1.5 Gy. noncancer diseases. 1.e.. the relationship is essentially independent of LET. dose rate and shape of the original dose-response curve. However. this use of “biological markers” cannot in any way be compared to their high precision use. described above, with noncancer disease. The principal reasonis that. while chromosome aberrations are due to intracellular DNA changes. and while their increase may well be proportional to whatever gene change or changes maybe directly causative with respect to a given cancer. neither the fraction of cells with at least one observable chromosomal aberration. northe total Relationship between incidence of solid tumors and chromosome aberrations in A-bormb survivors (both cities combined) 7.0 y = 5.3309e0-2 + 7.2687x R*2 = 0.964 Excess relative risk (irom Thompson et al. 1994) However. few successes have been achieved to date. and these not with radiation-ex posure o.8 0.0 r o.03 o.1 T 2.15 o.2 Fraction of cells with aberrations (estimated trom data in Preston et al. 1989) Fig. 8. Pilot showing the linear relationship between the fraction of cells with chromosomal! aberrations and the excess relative risk of solid tumors. Bond numt sure | valu Furth difte 0.1.0 used than: any ¢ the 1 ler usefi cance: syste mine the t time chan throu pote: ical ing | indi takir ing ¢ ence rega to Fi inter has t and vide deve suck sho. of st exc absc This with suct cell ora rate cal} hyp can dos: eve (fro