Gene locus mutation

Having briefly defined these four endpoints, I would like to ask, Are they related to known human disease Can they be measured quantitatively and Can they be measured with facility for inclusion in an overall plan for environmental bioassay Table I lists examples of gene locus mutations resulting in human disease phenylketonuria, histidinemia, Hartnup disease, and cvstinuria. Phenvlketonuria is... 

Examples of Human Gene Locus Mutation (from Vogel [5])... 

These very unfortunate syndromes do not occur at frequencies of one in 10,000 or one in 30,000 they are occurring on the order of one in 500 to one in, say, 2,000. Again, if you add together the several hundreds of human syndromes that are apparently caused by chromosome aberration, you discover a very expensive public health problem. I cannot offer any references to good estimates, but it seems that the total misery inflicted on the human population by chromosome aberration is approximately equal to that Inflicted by gene locus mutation. 

The nature of the toxicological endpoint to be measured. Some endpoints are more readily measured in certain cell types or cell lines. For example, the human hepatoma cell line HepG2 forms colonies with very low efficiency. Therefore some genetic toxicology assays, such as the induction of gene locus mutations, cannot be easily measured in this cell line. 

Human lymphoblasts Gene locus mutation No data - Penman and Crespi 1987... 

Gene-Locus Mutation Assays in Diploid Human Lymphoblast Lines... 

Several mammalian cell systems have been developed in order to determine the potential of food additives and other environmental chemicals to cause gene locus mutations. Some employ rodent cells, as described by Clive and Spector , whereas others use diploid human lymphoblasts as indicator organisms The human lymphoblast system measures the response of hypoxanthine guanine phosphoribosyl transferase (hgprt). Considerable care must be used with these systems for example, the importance of phenotypic lag has been clearly demonstrated by Penman and Thilly. ... 

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