Human gene mapping and cancer biology.
The topics covered in this paper include: (i) a somatic cell genetics approach for measuring the individual variability in the susceptibility to DNA damage/repair at the level of specific chromosomal sites; (ii) a rationale for a selective chemotherapy and/or immunotherapy of chromosomally unbalanced tumours; and (iii) studies on complementation for sister chromatid exchange (SCE) in roden-human hybrids. Preliminary studies indicate that the 'radiation co-transfer method' for gene mapping can be simplified and used in screening for differences in individual susceptibility to radiation induced chromosomal damage. The second topic is dealt with only speculatively, with the explicit aim of emphasizing a practical application in clinical medicine which may potentially derive from the admittedly esoteric activity of gene mappers. The third topic summarizes a somatic cell genetic approach to the study of SCE in mammalian cells. The high rate of SCE observed in an established rodent cell line can be fully suppressed after hybridization with SCE-normal human cells. However, this suppression can be fully removed after extensive loss of the human chromosome complement. Correspondingly, the high SCE rate of Bloom syndrome cells is fully corrected after hybridization with a Chinese hamster line, though the chromosomes of the latter parental cells continue to exhibit in the hybrid cells the moderately high rate of SCE which is typical of this animal line. These complementation experiments indicate that more than one lesion can upset the normal chromatid replication of mammalian cells and lead to high SCE. The experimental studies described promise to be of significant help for studies on the biology of SCE in general and offer a suitable way of screening for possible genetical heterogeneity among different Bloom syndrome patients.