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Inactivation of Ultraviolet Repair in Normal and Xeroderma Pigmentosum Cells by Methyl Methanesulfonate¹

Laboratory of Radiobiology and Environmental Health, University of California, San Francisco, San Francisco, California 94143

Excision repair of ultraviolet damage in the DNA of normal and xeroderma pigmentosum (Groups C, D, and variant) cells was inactivated by exposure of cells to methyl methanesulfonate immediately before irradiation independent of the presence of 0 to 10% fetal calf serum. The inactivation could be represented by a semilog relationship between the amount of repair and methyl methanesulfonate concentration up to approximately 5 mM. The inactivation can be considered to occur as the result of alkylation of a large (about 10⁶ daltons) repair enzyme complex, and the dose required to reduce repair to 37% for most cell types was between 4 and 7 mM. No consistent, large difference in sensitivity to methyl methanesulfonate was found in any xeroderma pigmentosum complementation group compared to normal cells, implying that reduced repair in these groups may be caused by small inherited changes in the amino acid composition (i.e., point mutations or small deletions) rather than by losses of major components of the repair enzyme complex.

¹ This work was supported by the United States Department of Energy.

² To whom requests for reprints should be addressed.

Received 8/ 4/81. Accepted 11/30/81.

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