Further Uses of Lymphoblast Assays

Further Uses of Lymphoblast Assays 6.2.1. Mutagenic Mechanisms 

Lymphoblast assays are tools for understanding the basic mechanisms of cellular mutation. We know that subpopulations (presumably mutants) of lymphoblasts resist alkylating agents. The mechanism of this resistance does not appear to involve cellular uptake. The increased resistance to alkylating agents could be caused by some DNA repair phenomenon or by the overproduction of some nucleophilic molecule that then acts as a scavenger. In any case, determining the mechanism of resistance could illuminate the mechanism of chemical mutation in human cells. 

It is now possible to correlate the formation of specific DNA adducts and mutation in human cells. Experiments with the mycotoxin aflatoxin Bi have been completed and indicate that the probability of a covalently bound aflatoxin molecule, giving rise to a mutation to 6TG resistance, is about 1/200. We are also studying UV-induced dimer formation and DNA repair in relation to mutation in human lymphoblasts. 

The most obvious use of human lymphoblast assays is to screen environmental chemicals or industrial effluents for their mutagenic effects. The techniques presented in this chapter are suitable for this purpose, at least in a qualitative sense. These facile assays answer the question of whether a particular chemical or complex mixture can cause mutation in human cells. We believe that this finding is a potentially important advance. Our work is still in the developmental stage, however, and the practical limitations of cell culture mutation assays must be overcome before they can equal or surpass the present ease and economy of bacterial mutation assays. 

We still need quantitative mutation data. The lymphoblast assays we have developed are quantitative and apparently unbiased. Whether mutation in lymphoblasts accurately reflects mutation in other human cells is an open question. There are not yet enough data to make any meaningful comparisons. 

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