Mouse mo-2 macrosatellites consisting of 31-bp tandem repeat units are mainly located at two loci in the C57BL/6 genome, one being at the centromere-distal telomeric region of chromosome 9 and the other at the pseudoautosomal (PA) region of chromosomes X and Y. The two clusters constitute approximately 300 kb and 150 kb, respectively. Southern analysis of a methylation-sensitive enzyme, HpaII-digested DNA showed that the mo-2 macrosatellites are detected as more than 30 polymorphic bands. Comparison of those bands between reciprocally crossed F1 mice revealed that approximately 20% of the allele-specific fragments exhibit different band intensities depending on the sex of the parent of origin. The differential methylation is observed in the mo-2 macrosatellite on the PA region but not in that on chromosome 9. Several fragments including the 3.4-kb fragment without internal HpaII site are more clearly detected when paternally derived, suggesting that the male-derived macrosatellite is undermethylated. Interestingly, the difference is much more remarkable in inter-subspecific F1 mice between C57BL/6 and MSM than F1 between C57BL/6 and C3H/He. This suggests the presence of a modifier(s) that affect(s) the methylation of mo-2 in the MSM genome.

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Quercetin, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), and okadaic acid are found in various foods and have been shown to have mutagenic or promoter-like activity. The effects of these three compounds on the transmission of the inactive X chromosome were examined in MST-C6 murine tumor cells, which were derived from hybrid F1 mice from matings between C57BL/6 and MSM mice. Polymerase chain reaction analysis using polymorphic markers on the X chromosome detected transmission distortion of the inactive X chromosome due to nondisjunction as a copy-number imbalance in allelic bands. The cells exposed to all three chemicals (but not untreated cells) exhibited such imbalances at high frequencies under exposure conditions similar to those in previous experiments in which tumor progression and recombination were observed. The cells also showed increased frequencies of tumor formation when subcutaneously injected. These results suggest that the three chemicals are capable of inducing transmission distortion of the inactive X chromosome and that such activity may be a causative factor in promoting the tumorigenicity of MST-C6 cells.