( Measure mutations in any tissue w...)Tissue Specificity for Mutation Parallels Tissue Specificity for Cancer

Measure mutations in any tissue with the Big Blue transgenic rodent mutation assay

Johan G. de Boer Barry W. Glickman
Centre for Environmental Health, University of Victoria, Victoria, BC Canada

With Stratagenes Big Blue transgenic rodent mutation assay,* which carries the E. coli lacI transgene in a retrievable chromosomally integrated shuttle vector, it is easy to study mutations in male and female mice or rats of any age under selected conditions in vivo. Multilab studies indicate that mutations are generally induced in the same tissue that tumors are produced but not in nontarget tissues. This makes the transgenic model for the study of genotoxicity even more valuable, since mutations can be studied in virtually any tissue.

The hallmark of occupational- and lifestyle-related cancer is tissue specificity. Human exposures to carcinogens result in particular types of cancer at predictable sites; tobacco smoke, arsenic, and ionizing radiation all produce their own unique kinds of cancers in preferred tissues. Tissue specificity is also a feature of animal model systems. For example, when male mice are exposed to the flame retardant tris(2,3-dibromopropyl)phosphate (TDBP), they contract kidney tumors, and the alkylating agent dimethylnitrosamine predominantly produces liver, kidney, and lung tumors. Sex can also have an impact on tissue targeting. In the case of TDBP, liver tumors predominate in female mice, while kidney tumors are seen in male mice.

Figure 1

This kind of information is crucial for identifying suspected carcinogens. Hence, we ask a critical question: Does mutation follow the same pattern as the targeting of tumors? In other words, are mutations being induced in tissues where tumors are recovere
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