MYCOPLASMAS AND ONCOGENESIS - PERSISTENT INFECTION AND MULTISTAGE MALIGNANT TRANSFORMATION

Oncogenic potential of human mycoplasmas was studied using cultured mo use embryo cells, C3H/10T1/2 (C3H). Mycoplasma fermentans and Mycoplas ma penetrans, mycoplasmas found in unusually high frequencies among pa tients with AIDS, were examined. Instead of acute transformation, a mu ltistage process in promotion and progression of malignant cell transf ormation with long latency was noted; after 6 passages (1 wk per passa ge) of persistent infection with M. fermentans, C3H cells exhibited ph enotypic changes with malignant characteristics that became progressiv ely more prominent with further prolonged infection, Up to at least th e 11th passage, all malignant changes were reversible if mycoplasmas w ere eradicated by antibiotic treatment, Further persistent infection w ith the mycoplasmas until 18 passages resulted in an irreversible form of transformation that included the ability to form tumors in animals and high soft agar cloning efficiency, Whereas chromosomal loss and t ranslocational changes in C3H cells infected by either mycoplasma duri ng the reversible stage were not prominent, the onset of the irreversi ble phase of transformation coincided with such karyotypic alteration, Genetic instability-i.e., prominent chromosomal alteration of permane ntly transformed cells-was most likely caused by mutation of a gene(s) responsible for fidelity of DNA replication or repair, Once induced, chromosomal alterations continued to accumulate both in cultured cells and in animals without the continued presence of the transforming mic robes, Mycoplasma-mediated multistage oncogenesis exhibited here share s many characteristics found in the development of human cancer.