Abstract
A VLDL-associated cytotoxic factor was isolated from sera of pregnant rats and characterized. The inhibitory effect of this factor on the macromolecular synthesis of rat prostate adenocarcinoma cells (PA-III) was also examined. VLDL (Sf 20-400) was subfractionated by differential ultracentrifugal flotation and the Sf 100-400 fraction was associated with most of the oncolytic activity. Chemical analysis of serum VLDL at various stages of pregnancy indicated that the 4 major constituents of VLDL (protein, triglyceride, cholesterol, and phospholipid), and the cytotoxic titre, were increased significantly before parturition and restored to normal levels by 24 h post partum. The delipidation of lyophilized VLDL by n-heptane suggested that the cytotoxic component was associated with the neutral lipid core of VLDL. Kinetic studies of colony inhibition and the incorporation of radioactive thymidine and leucine into 10% TCA precipitates of PA-III cells showed that VLDL induced irreparable cellular damage during the initial 15 h of incubation. The cytotoxic activity of VLDL was not due to the association with PGF2 alpha, beta-oestradiol, progesterone, 25-hydroxycholesterol, or free fatty acids (oleic, stearic, palmitic, linoleic, linolenic and arachidonic acids), monopalmitolein, elaidyl and alpha-linolenyl alcohol. The role of this factor in host defence against neoplasia is discussed.
Highlights
Summary.-A very-low-density lipoproteins (VLDL)-associated cytotoxic factor was isolated from sera of pregnant rats and characterized
Kinetic studies of colony inhibition and the incorporation of radioactive thymidine and leucine into 10% TCA precipitates of PA-III cells showed that VLDL induced irreparable cellular damage during the initial 15 h of incubation
The concept that lipoproteins can function as containment factors in host defence against neoplasia was developed and substantiated with the observation that very-low-density lipoproteins (VLDL), isolated from sera of pregnant rats, manifest a wide spectrum of cytotoxicity against a number of tumour cell lines (Chan & Pollard, 1978a, b)
Summary
Volume), dried and transferred to another tank containing diethyl ether-hexane 6:94. Animals and serum collection.-The Lobund and developed to within 1 cm of the top of Wistar (LoW) rats (150-200 g), used through- the plate (Freeman & West, 1966). The npH 7-0) of density 1006 was layered carefully heptane extracts were pooled and evaporated over 4 ml of serum in a Beckman poly- under N2 to a final volume of 1 ml for lipid carbonate centrifuge tube. POLLARD (Chang & Pollard, 1977; Chan, 1981) were Millipore filters (HAWPO 2500) and counted used as target cells to investigate the onco- in Biofluor, a Beckman LS 7000 liquidlytic activity of VLDL. Both lines have been scintillation counter being used. Cloned and reconstitute adenocarcinomas when inoculated into LoW rats, where they metastasize spontaneously via ipsilateral
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