(1983). Ionizing Radiation: Sources and Biological Effects. International Journal of Radiation Biology and Related Studies in Physics, Chemistry and Medicine: Vol. 43, No. 5, pp. 585-586.

Ionizing Radiation: Sources and Biological Effects

Summary Peripheral blood lymphocytes of patients with Fanconi9s anemia (FA) were tested for their susceptibility to chromosome breakage by caffeine, chloramphenicol, actinomycin D, methylmethanesulfonate, nitrogen mustard, mitomycin C, decarbamoyl mitomycin C, N -methyl- N′ -nitro- N -nitrosoguanidine, 4-nitroquinoline 1-oxide, 8-methoxypsoralen, and 60 Co γ-ray and ultiviolet irradiations. A definitely abnormal response of the chromosomes of the FA cells was found when they were treated with nitrogen mustard and mitomycin C and after the irradiation with long-wavelength ultraviolet light in the presence of 8-methoxypsoralen. The specifically increased susceptibility to these compounds, which can introduce interstrand cross-links into DNA, is interpreted as an indication that the FA cells are defective in the repair mechanism to tolerate the cross-links produced in their DNA. The impairment of the capacity to tolerate the lesions produced in DNA may be implicated in the increased risk to develop malignant neoplasms in this hereditary disorder.

https://cancerres.aacrjournals.org/content/canres/33/8/1829.full.pdf

A high susceptibility of Fanconi's anemia to chromosome breakage by DNA cross-linking agents.

The first well-documented observation of retinoblastoma (Rb) in several members of one family was published by Lerche (1821). Four of seven siblings, children of healthy parents, were affected. At that time, the tumor almost invariably led to death during infancy or early childhood. The first pedigrees with transmission through two or more generations were observed only after enucleation of the affected eye had been introduced by von Graefe. More recently, the mode of inheritance has been identified as autosomal dominant with incomplete penetrance; Fig. 13.1 shows a typical pedigree. Unilateral as well as bilateral cases may occur in the same family, and the tumor may even skip one generation. Statistical analysis of many families (see Vogel 1979) led to the conclusion that the penetrance of the dominant gene causing Rb is about 90%; i.e., 90% of heterozygotes will be affected.

Genetics of retinoblastoma

To estimate the leukemogenic potential of alkylating agents, we surveyed 70 institutions using these drugs for the frequency of second cancers in patients with advanced ovarian cancer. Thirteen cases of acute nonlymphocytic leukemia occurred among 5455 patients, as compared to 0.62 cases expected (relative risk = 21.0). All 13 had received alkylating agents. Nine also received radiotherapy. The relative risk for patients given chemotherapy was 36.1 and rose to 171.4 for those surviving for two years (rate = 13.75 per 1000 patients per year). To evaluate the role of therapy versus underlying disease, a historical control of 13,309 patients with ovarian cancer in the National Cancer Institute's End Results Program was analyzed. No excess of leukemia was noted in this group, even among 6596 women receiving radiation. The excess of acute nonlymphocytic leukemia, therefore, appears attribute to alkylating agents, although the effect may be enhanced by exposure to radiation, as previously suggested for Hodgkin's disease.

https://www.nejm.org/doi/pdf/10.1056/NEJM197707282970402?listPDF=true

Acute leukemia after alkylating-agent therapy of ovarian cancer

Mutation is one of the basic phenomena of life. Without mutation, the gradual development of life from inorganic material would have been impossible, and the evolution of living beings from the first groups of molecules in which a primitive, information-carrying unit cooperated with an energy gaining device59 up to the present diversity of highly refined living organisms could not have occurred. Therefore, one would expect that mutation, and especially “spontaneous” mutation, i.e., that occurring naturally and without any detectable external reasons, would attract the research activity of many biologists, especially geneticists. Surprisingly, however, this is not the case. In most experimental studies—for example, on microorganisms, Drosophila or the mouse—research on spontaneous mutation is being carried out more or less as a sideline of other work, and the results are widely scattered.

Renate Kurth

Papers

Spontaneous chromosomal breakage and high incidence of leukemia in inherited disease.