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Expression of the Endogenous 0⁶-Methylguanine-DNA-methyltransferase Protects Chinese Hamster Ovary Cells from Spontaneous G:C to A:T Transitions¹

Laboratory of Comparative Toxicology and Ecotoxicology, Istituto Superiore di Sanitá, 00161 Rome, Italy [G. A., R. B., E. D., M. B.], and Clare Hall Laboratories, Imperial Cancer Research Fund, South Mimms, UK [M. M.]

² To whom requests for reprints should be addressed, at Laboratory of Comparative Toxicology and Ecotoxicology, Istituto Superiore di Sanitá, Viale Regina Elena 299, 00161 Rome, Italy.

We have investigated whether the presence of a DNA repair enzyme, 0⁶-methylguanine-DNA-methyltransferase (MGMT), affects the nature of spontaneous mutations in a mammalian cell line. We compared spontaneous mutations in the adenine phosphoribosyl transferase gene of a Chinese hamster ovary (CHO) cell line that expressed 14,000 MGMT molecules/cell with those in the parental CHO cells lacking this DNA repair activity. The mutation rate/cell/generation of the two CHO cell lines did not differ significantly. However, DNA sequence analysis of spontaneous mutations in the MGMT-proficient CHO cell line revealed a complex picture. No significant difference from the parental CHO cells was found in the number or type of deletions, frame-shifts, multiple substitutions, or insertions. The frequency of G:C to T:A transversions was elevated in MGMT-proficient CHO cells. Expression of the enzyme considerably reduced G:C to A:T transitions (25% versus 8.3%). This latter result is the first evidence that this protein is active on an endogenous source of 0⁶-methylguanine that is normally responsible for spontaneous G:C to A:T transition mutations.

¹ This work was partially supported by European Economic Community Contract EV4V-0044-I (A) and by a joint Royal Society/Consiglio Nazionale delle Ricerche grant.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 5/11/92. Accepted 9/22/92.

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