John H. Frenster, Sharon R. Landrum, Marilyn A. Masek, and Shirley L. Nakatsu
Department of Medicine, Stanford University, Stanford, Calif. 94305
Abstract:
Carcinogenic chemicals, oncogenic viruses, and steroid hormones all prefer to bind to single-stranded DNA portions of the host cell genome (Cancer Res. 36: 3394 (1976). Localized DNA helix openings provide short lengths of such single-stranded DNA, and are necessary to permit the induction of gene de-repression characteristic of human neoplasms (Nature 269: 752 (1977). We have developed a high-resolution electron microscopic technique for directly analyzing DNA helix openings within living cells (J. Natl. Cancer Inst. 59: 839 (1977), and have quantitated this technique for use within individual cells undergoing cell differentiation within human bone marrow. A total of 536 normal in-vivo differentiating bone marrow cells were analyzed. DNA helix openings were found only within the extended 10 millimicron-diameter microfibrils of the active euchromatin portion of the cell nuclei, and ranged in length from 25-700 millimicrons, corresponding to 70-2000 base pairs in DNA helix length. During the course of in-vivo cell differentiation within human bone marrow, these DNA helix openings were observed to decrease in both size and number per cell, correlating with the known decreased rate of neoplastic transformation occuring in cells undergoing cell differentiation and maturation. These DNA helix openings were found to be asymmetrically distributed within the cell nuclei, with the majority of the DNA helix openings being found in that half of the cell nucleus closest to the cell center, the endoplasmic reticulum, and the Golgi apparatus, organelles of the cytoplasm which are thought to be important in the cellular activation of carcinogenic chemicals and oncogenic viruses.
References:
1. Frenster JH, "Selective Control of DNA Helix Openings during Gene Regulation", Cancer Res: 36: 3394-3398 (September, 1976).
2. Kumakiri M, and Hashimoto K, "Acridine-Orange-DNA Complex in Actinic Keratosis", J. Natl. Cancer Inst. 59: 839-844 (September, 1977).
3. Shields R, "Gene De-Repression in Tumours", Nature 269: 752-753 (October 27, 1977).
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