Cytogenetic studies of chromosome aberrations.

Two papers appeared in a recent issue of Human Genetics which, if true, have important implications. However, I have serious concerns about the methodology and conclusions of both papers. The first of these papers is that of Goswami et al. (1990) entitled "Search for chromosomal variations among gas-exposed persons in Bhopal". The authors studied chromosome damage in three groups of patients, a control group of randomly selected individuals not exposed to methyl isocyanate (MIC), a second control group of individuals who were not themselves exposed to MIC but who had an exposed relative, and a group of 53 MIC exposed individuals. The slides from each group were scored blind. However, the account of the chromosome damage seen in both the control and exposed individuals is incomprehensible. It is customary when scoring chromosome damage to have a table with the total number of cells scored, the number of ceils showing one and two hit aberrations, the total number of aberrant cells and the number of aberrations per cell (Buckton and Evans 1973). None of this information is provided in the paper. The authors score a number of novel types of chromosome aberrations not normally produced by clastogen exposure none of which are defined; for example "marker dots", "Robertsonian translocations", "mosaic cells" and "premature centromere division". The meaning of some of these is clear from other contexts but the meaning of others, such as mosaic cells, is obscure. The authors provide us with two illustrations, presumably of their best preparations (none of us illustrate papers with our worst preparations!). Both are of very poor quality and neither illustrate the cytogenetic phenomena that they purport to. Figure 1 shows examples of satellite associations, not Robertsonian translocations, and the chromosomes are numbered in spite of the fact that it is not possible to separately identify chromosome pairs in a preparation of this quality. Figure 2 shows a purportedly deleted chromosome 5 which is a chromosome 11, a deleted chromosome 9 which is a chromosome 12, and a chromatid deletion which appears to be a twisted chromatid. It is apparent, both from the way that the data are presented and the standard of the illustrations, that the authors of this paper are familiar neither with human chromosome morphology nor with the nature of chromosome damage and the way it is scored. Therefore their conclusions cannot be accepted. The second paper is by Eva van den Berg-de Ruiter and her colleagues (1990) entitled "Chromosomal damage in peripheral blood lymphocytes of patients treated for testicular cancer". In this paper chromosome damage was scored in blood leucocytes from a series of patients with testicular cancer. Twenty six patients having had surgery alone while 35 patients had surgery followed by chemotherapy. Chromosome damage was purportedly found in both series of patients at similar frequencies. This observation leads the authors to conclude that some patients exhibit genetic instability which predisposes them to the development of malignancy. Unfortunately there were no controls and therefore: (1) there is no information on the level of damage in patients who do not have a malignancy and (2) the preparations could not be scored in a blind fashion. Furthermore, while the authors report every single abnormal cell, the great majority do not show chromosome damage but merely have missing chromosomes. The most reasonable explanation for the observations is that the preparations contain a large number of broken cells. The conclusions in this paper cannot be accepted in the absence of control observations, blind analysis and conventional aberration scoring.