The Conditional Mutator Phenotype in Human Tumor Cells: Correction

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Science  29 Jan 1999:
Vol. 283, Issue 5402, pp. 639d
DOI: 10.1126/science.283.5402.639d

In a previous report, “Conditional mutator phenotypes in hMSH2-deficient tumor cell lines” (5 Sept. 1997, p. 1523) (1), some of us (B.R. and M.M.) demonstrated that two hMSH2-deficient tumor cell lines exhibited a conditional mutator phenotype. When the cells were kept in a growing state, mutation rates were low. However, when the cells were allowed to come to confluence and stand in high-density, suboptimal growth conditions, the mutant frequency increased as much as 7900-fold. We suggested that this increase might have been the result of an accumulation of mutations occurring while the cells were maintained in suboptimal culture conditions.

An alternative explanation for the differences in mutant frequencies is suggested by more recent experiments. When these tumor cell lines were grown in medium supplemented with a new serum batch, both log-growing and high-density cultures displayed a high mutant frequency. To confirm that the serum was the component of the medium that led to the changes in mutant frequency, we grew cells from the same inoculum side by side in medium supplemented with our original serum or in medium supplemented with the new batch. Cells grown in our original serum showed a low mutant frequency, while those grown in the new batch had a substantially (>2000-fold) elevated frequency. When cells were grown in mixtures of the two kinds of serum, mutant frequency was again low. These data argue that the conditional mutator phenotype is the result of suppression of mutation in log-growing cells by factors in the original serum. Since high-density cultures accumulate mutations, we suggest that high-density cultures may not respond to this suppressive mechanism or that the factor responsible for suppression may become exhausted in the medium. Nevertheless these data demonstrate that serum factors may play an important role in governing mutation rate in some tumor cells.

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