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Tissue Specificity for Mutation Parallels Tissue Specificity for Cancer

tica">Heart

Ethylene oxide7

lung

lung

Spleen, bone marrow, germ cells

Benzene8

Lung, leukemia, lymphomas

Lung, spleen

liver

* De Boer et al., unpublished
See text for additional details.

TDBP

The flame retardant tris(2,3-dibromopropyl)phosphate (TDBP) is an established kidney-specific carcinogen in male and female rats and male mice; in female mice, it targets the liver. In a TDBP study,1 the lacI mutation frequency was determined in the kidney, liver, and stomach of male Big Blue mice after treatment with 2000 ppm of TDBP. The mutant frequency increased marginally in the kidney and liver (approximately 50%) but not the stomach. Sequencing the mutants revealed a unique difference in mutational spectrum: The spectrum from the liver was indistinguishable from that of untreated animals, while that from the kidney included unique deletions of single GC base pairs. Thus, in this case, TDBP-specific mutations were induced only in the tissue where tumors were recovered. Hence, DNA sequencing can improve the assay sensitivity in situations where the induced mutant frequency is low.

DMN

Tissue specificity was also observed with dimethylnitrosamine (DMN), which has been well studied in the liver.2 DMN produces tumors in various organs including the liver, kidney, and lung. Suzuki et al.3 observed mutation induction in each of these tissues (6
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