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Elevated Mutant Frequencies in Lymphoid Tissues Persist throughout Plasmacytoma Development in BALB/c.LIZ Mice¹

Laboratory of Genetics, Division of Basic Sciences, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255 [K. F., K. A. K., S. J.], and Institut für Klinische Molekularbiologie and Tumorgenetik, GSF, D-81377 Munich, Germany [G-W. B.]

Using the phage LIZ-based transgenic in vivo mutagenesis assay, the mean mutant frequencies in the target gene, lacI, were found to be significantly increased in lymphoid tissues of congenic BALB/c.LIZ N₅ mice in the terminal stage of a plasmacytoma induction experiment, 213–280 days after the first i.p. injection of the plasmacytomagenic agent pristane (2,6,10,14-tetramethylpentadecane). In plasmacytoma-bearing mice (n = 7), mutant frequencies in the spleens and mesenteric lymph nodes were elevated 2.46-fold and 5.35-fold, respectively, when compared with age-matched controls. In plasmacytoma-negative mice (n = 11), mutant frequencies were increased 2.30-fold (spleens) and 3.48-fold (mesenteric nodes). These results, interpreted in conjunction with our previous findings (K. Felix et al., Cancer Res., 58: 1616–1619, 1998) of approximately 3-fold elevations in pristane-induced splenic mutagenesis on day 42 postpristane, indicate that increased mutant levels in lymphoid tissues persist throughout plasmacytomagenesis in genetically susceptible BALB/c mice.

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