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Molecular and Cellular Biology, December 1999, p. 7995-8002, Vol. 19, No. 12
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Mycoplasmal Infections Prevent Apoptosis and Induce Malignant Transformation of Interleukin-3-Dependent 32D Hematopoietic Cells

Shaw-Huey Feng, Shien Tsai, Jose Rodriguez, and Shyh-Ching Lo*

American Registry of Pathology, Department of Infectious and Parasitic Disease Pathology, Armed Forces Institute of Pathology, Washington, D.C. 20306

Received 15 July 1999/Returned for modification 18 August 1999/Accepted 30 August 1999

32D cells, a murine myeloid cell line, rapidly undergo apoptosis upon withdrawal of interleukin-3 (IL-3) supplement in culture. We found that 32D cells, if infected by several species of human mycoplasmas that rapidly activated NF-kappa B, would live and continue to grow in IL-3-depleted culture. Mycoplasma-infected cells showed no evidence of autocrine production of IL-3. Pyrrolidine dithiocarbamate (PDTC) blocked activation of NF-kappa B and led to prominent cell death. Heat-killed mycoplasmas or mycoplasmal membrane preparations alone could support continued growth of 32D cells in culture without IL-3 supplement for a substantial period of time. However, upon removal of heat-inactivated mycoplasmas, 32D cells quickly became apoptotic. In comparison, live Mycoplasma fermentans or M. penetrans infection for 4 to 5 weeks induced malignant transformation of 32D cells. Transformed 32D cells grew autonomously and no longer required support of growth-stimulating factors including IL-3 and mycoplasmas. The transformed 32D cells quickly formed tumors when injected into nude mice. Karyotyping showed that development of chromosomal changes and trisomy 19 was often associated with malignant transformation and tumorigenicity of 32D cells. Mycoplasmal infections apparently affected the fidelity of genomic transmission in cell division as well as checkpoints coordinating the progression of cell cycle events.

* Corresponding author. Mailing address: Department of Infectious and Parasitic Disease Pathology, Armed Forces Institute of Pathology, Building 54, Room 4091, 14th St. and Alaska Ave., NW, Washington, DC 20306-6000. Phone: (202) 782-1870. Fax: (202) 782-7477. E-mail: los{at}afip.osd.mil.

Molecular and Cellular Biology, December 1999, p. 7995-8002, Vol. 19, No. 12
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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