I. Effect of Cellular Genotype: Homozygous Strains

The specific catalase activity of human diploid cell strains increases with progressive growth of the culture, and falls again following subculture. Although the increase is small, it is readily demonstrable, and is exponential with time. The response of catalase activity to progressive growth of the culture was studied in three abnormal human cell lines. A diploid cell strain, developed from a patient homozygous for the gene causing acatalasia I, had no detectable catalase activity throughout the life cycle of the culture. Another diploid cell strain, developed from a patient homozygous for the gene causing acatalasia 11, had about 5% normal catalase activity, but the proportionate increase in specific activity as the culture grew was the same as for normal cells. Thus the mutation causing acatalasia I1 does not change the responsiveness of the cell in terms of catalase activity to progressive growth of the culture. The behavior of a heteroploid line was similar to that of the normal diploid strains, but when the growth of the heteroploid cultures reached a plateau, their population densities were four times higher than those of the diploid strains and they had about twice the specific catalase activity. In 1960 Weisman, Smellie, and Paul (‘60) reported that the specific thymidine kinase activity of Gcells, a heteroploid mouse line, changed as the culture grew. Since then a number of other cases have been reported (table 1) where specific activity total enzyme activity in the culture divided by total cell protein was found to change during growth. We have examined the enzyme catalase from this standpoint in human diploid cell strains. The purposes of the present paper are : 1. To describe the change in specific catalase activity as cultures of diploid cells grow. 2. To contrast the change in catalase activity with growth in normal cells and in cells carrying mutant Mendelian genes which affect catalase activity. 3. To contrast the change in catalase activity in human diploid cell strains with a human heteroploid line during growth. The mutant Mendelian genes studied are the ones causing acatalasia I and acatalasia II. Acatalasia I is a recessive abnormality observed in a small number of Japanese and Korean families (Takahara, ’52; Wyngaarden and Howell, ’66). Diploid cell strains from affected persons have a defiJ. CELL. PHYSXOL., 71: 151-160. ciency of catalase activity (Krooth, Howell and Hamilton, ’62; Kitamura, Ogata and Takahara, ‘62; Takahara, Sadamoto and Ogata, ’66). Acatalasia I1 has been observed in several Swiss families; the erythrocytes and diploid cell strains of homozygous persons are reported to have about 15% normal catalase activity. (Aebi, Baggiolini, Dewald, Lauber, Suter, Micheli, Frei, ’64).