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Association of Elevated Mutagenesis in the Spleen with Genetic Susceptibility to Induced Plasmacytoma Development in Mice¹

Laboratory of Genetics, DBS, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255 [K. F., K. K., S. J.], and Institut für Klinische Molekularbiologie and Tumorgenetik, GSF, Munich, Germany [K. F., G-W. B.]

Using the phage LIZ-based transgenic in vivo mutagenesis assay, mean mutant rates were determined in the spleen of mice exposed to sustained oxidative stress and were found to be increased approximately 3-fold in plasmacytoma-susceptible BALB/c and C.D2-Idh1-Pep3 mice, but not in plasmacytoma-resistant DBA/2N mice. This finding suggests a correlation between the genetic susceptibility to inflammation-induced peritoneal plasmacytomagenesis and the phenotype of increased mutagenesis in lymphoid tissues, raising the possibility that plasmacytoma resistance genes may inhibit tumor development by minimizing oxidative mutagenesis in B cells.

¹ Supported in part by a grant from the Mildred-Scheel-Stiftung for cancer research (to G-W. B.).

² To whom requests for reprints should be addressed, at Laboratory of Genetics, National Cancer Institute, NIH, Building 37, Room 2B03, Bethesda, MD 20892-4255. Phone: (301) 496-2101; Fax: (301) 402-1031; E-mail: felixk@dc37a.nci.nih.gov.

Received 1/22/98. Accepted 3/ 3/98.

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