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Studies on Chemically Induced and "Spontaneous" Alterations of Morphology and Growth Potential in Human Cell Culture^*

( Reuben Peterson Memorial Research Laboratory, Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan)

Morphologic alterations of fibroblastic-like cells to epithelial-like forms were chemically induced in monolayer cultures derived from normal and malignant tissues of the human female genital system. These sudden and irreversible changes occurred at subculture when the cultures were treated with a trypsin-antibiotic solution for 2–5 minutes. The unusual features of the chemical process which clearly distinguished it from the frequently reported "spontaneous" alteration phenomenon were (a) the requirement for young, actively multiplying cells, (b) the high percentage of cells altered, and (c) the speed of the reaction.

Studies were carried out to permit comparison of the chemical alterability of fibroblastic-like cultures with their ability to undergo a "spontaneous" type "transformation." In a series of 51 normal and malignant tissues, 24 were chemically altered, while 25 underwent "spontaneous" change. Significantly, only ten specimens were capable of undergoing both types of alteration response. Although both conversion processes led without exception to the establishment of epithelioid cell strains with the capacity to survive indefinitely, the evidence suggested that there is no direct relationship between the two alteration phenomena.

Fibroblastic-like cells derived from cancer tissues were equally susceptible to either alteration response, whereas similar cells derived from normal tissues were significantly more prone to undergo "spontaneous" conversion than to be altered chemically.

The possible origins of the alterable cells and the mechanisms of the two alteration phenomena are discussed with reference to their implications in the problem of carcinogenesis.

^* This work was supported by grant C-3112 from the National Institutes of Health, USPHS. Presented, in part, before The Tissue Culture Association, Detroit, Michigan, June, 1961.

Received 12/ 8/61.