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Altered Growth Properties of Chinese Hamster Cells Exposed to 1-Methylguanine and 7-Methylguanine¹

Department of Biochemistry, University of Colorado Medical Center, Denver, Colorado 80262

Primary Chinese hamster embryo cell cultures generally yield cell lines with a finite lifetime in culture. However, if early-passage cells are exposed chronically to either of two normal degradation products of transfer RNA, 1-methylguanine or 7-methylguanine, they are converted to continuous lines with altered growth characteristics and morphology. The continuous cell lines have saturation densities 2- to 10-fold higher than did finite control cultures, and some have the ability to grow in soft agar. Certain cultures have the general appearance of fibroblasts while others are more epithelial-like. Quantitative and qualitative alterations in the transfer RNA methyltransferases are early markers for neoplastic transformation in vivo and in vitro. Transfer RNA methyltransferase activity in the continuous lines is elevated compared to that of finite Chinese hamster cells. Neoplastic transformation has been demonstrated for a 1-methylguanine-derived line, and both 1-methylguanine- and 7-methylguanine-treated cell lines exhibit characteristics similar to those of Chinese hamster cells transformed with the carcinogen 3,4-benzopyrene or the DNA tumor virus SV40.

¹ Supported in part by Contract CM-12186 and Grants CA-05441 and CA-12742 awarded by the National Cancer Institute, Department of Health, Education, and Welfare.

² A Postdoctoral Fellowship Awardee of the National Cancer Institute.

³ To whom requests for reprints should be addressed.

Received 8/15/77. Accepted 4/27/78.