O6-methylguanine-DNA methyltransferase content in human lymphocytes following surgical trauma.

O6-methylguanine-DNA methyltransferase removes methyl groups from the O-6 position of guanine in DNA previously alkylated by alkylating carcinogens. Thus, the protein facilitates restoration of the impaired DNA. The content of O6-methylguanine-DNA methyltransferase was assayed in circulating lymphocytes and the impact of surgical trauma investigated. Patients (n = 13) without metabolic diseases admitted for elective orthopedic surgery were used. The patients were allowed water and food postoperatively. Blood was taken before and 3 days following surgery and the circulating lymphocytes were isolated. Before surgery, the O6-methylguanine-DNA methyltransferase content determined in the cell extracts showed patient-specific variations. Following surgery, a significant decrease of the protein by 60% (from 609 to 243 fmole/mg of DNA) was observed. The intensity of surgical trauma was confirmed by the decrease in plasma albumin concentration and the increase in white blood cell counts. The surgical trauma might elicit its effect as either a change in turnover of O6-methylguanine-DNA methyltransferase or a release from the thymus of lymphocytes low in enzyme levels. In summary, the surgical trauma per se was the cause of the pronounced decrease in the O6-methylguanine-DNA methyltransferase seen here. Investigations on O6-methylguanine-DNA methyltransferase levels have an important relevance in studies on tumor-promoting agents inhaled and then taken up by the T lymphocytes of prospective proliferating capacity.