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Immortalization and Transformation Are Associated with Specific Alterations in Choline Metabolism¹

The Royal College of Surgeons Unit of Biophysics, Institute of Child Health, 30 Guilford Street, London WC1N 1EH, United Kingdom [K.K.B., S.R.W., C. L. F.]; Imperial Cancer Research Fund, Lincoln's Inn Fields, London WC2A 3PX, United Kingdom [H. L.]; and Huntsman Cancer Institute, Salt Lake City, Utah 84112 [M. D. N.]

Analysis of transformed, immortalized, and primary rat Schwann cells by high-resolution proton nuclear magnetic resonance spectroscopy reveals that immortalization of Schwann cells (by SV40 large T antigen) induced a decrease in sn-glycero-3-phosphocholine (GPCho), whereas H-ras alone, which is known to cause growth arrest in these cells, induced a marked increase in GPCho and a decrease in phosphocholine (PCho). An increase of PCho was found only in cells fully transformed by both oncogenes together. Moreover, we examined 11 human tumor cell lines, all of which expressed a PCho:GPCho ratio similar to that of fully transformed rat Schwann cells. Importantly, neither the absolute levels of PCho nor the ratio of PCho:GPCho were correlated with the rate of cell division across a range of normal (primary cultures) and transformed cells. Thus, raised PCho:GPCho ratios may serve as an indicator of multiple oncogenic lesions and malignancy in noninvasive tumor investigations.

¹ Supported by the Wellcome Trust and Cancer Research Campaign.

² To whom requests for reprints should be addressed. Phone: 44-171-242-9789, extension 2191; Fax: 44-171-813-0399; E-mail: K.Bhakoo@ich.ucl.ac.uk.

Received 5/16/96. Accepted 8/ 8/96.

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