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Properties of the Accelerant Factor(s) for a Transplantable Mouse Mammary Tumor, Z8352^{* ,}

Howard H. Shear, Jerome T. Syverton and John J. Bittner

( Dept. of Bacteriology and Immunology and the Division of Cancer Biology, Dept. of Physiology, University of Minnesota, Minneapolis, Minn.)

An accelerant factor(s) derived from mouse mammary adenocarcinoma Z8352 which elicits enhancement of the malignant process, associated with the subsequent transplantation of viable tumor cells in susceptible mice, was the subject of physicochemical and serological studies. A tenfold, and possibly a 100-fold, dilution of accelerant material was capable of evoking enhancement. The active factor(s) was nondialyzable, retained by a Seitz EK filter disc, and associated with both the mitochondrial and microsomal fractions which had been obtained by subjecting "fresh accelerant" to differential ultracentrifugation. The enhancive activity of the accelerant factor(s) was independent of the thermolability of the cancer cells from which it was derived. Exposure for 30 minutes at 44° C., or higher, devitalized the Z8352 cancer cells; the accelerant factors were inactivated by similar exposure at 56° C. but not at 45° C. The activity of accelerant material was removed or destroyed by exposure to trichloroacetic acid, ether, or NaOH. Contrariwise, exposure to trypsin or HCl failed to inactivate the capacity to elicit transplant tumor enhancement. Finally, neither were antibodies as precipitins, evoked by the injection of fresh accelerant material into rabbits, capable of neutralizing the tumor-enhancive effect, nor were these antibodies upon serological precipitation capable of specifically removing the active factor(s).

^* This investigation was supported in part by a research grant from the National Cancer Institute of the National Institutes of Public Health, Public Health Service.

The material in this paper represents in part the thesis submitted by H. H. Shear in partial fulfillment of the requirements for the Ph.D. degree.

Predoctorate Research Fellow, National Cancer Institute, Public Health Service. Present address: Department of Bacteriology, University of Rochester, School of Medicine and Dentistry, Rochester, New York.

Received 10/ 1/53.