Decade of the brain: the gray area of research on gray matter.

Sir,-In a recent issue of this Journal Chan and Pollard (1981) report the characterization of a VLDL-associated cytotoxic factor. The cytotoxicity of VLDL was not due to a number of lipids carried by that lipoprotein, including saturated and unsaturated free fatty acids, unsaturated monoglycerides and alcohols, steroid hormones, prostaglan-dins and oxygenated derivatives of cholesterol such as 25-hydroxycholesterol. The data suggested that the cytotoxic component was associated with the neutral lipid core of VLDL, but its identity was not known.. The findings of Chan and Pollard may tentatively be interpreted as supporting our concept that VLDL is a major plasma transporter of lipophilic xenobiotics with cytotoxic and mutagenic/carcinogenic activities. In this connection it is noteworthy that LDL and HLD have no cytotoxicity (Chan & Pollard, 1978). In respect of the muta-genicity associated with plasma lipo-proteins it has been shown that in man (Rueff & Halpern, 1982) VLDL was the only mutagenic lipoprotein fraction in the Salmonella/mammalian microsome assay, and that the VLDL-associated muta-genicity was not due to triglycerides, but dependent on the particular exposure of the individual to mutagenic/carcinogenic compounds (e.g. smoking or occupational exposure to mineral oils) (Gomes & Rueff, unpublished). However, it has still to be decided whether our observation of the absence of mutagenicity of LDL and HDL can be explained by any metabolic mechanism. In fact, it has been demonstrated (Shu & Nichols, 1979) that benzo-(a)pyrene preferentially associates in human plasma in vitro with VLDL and LDL, but to a lesser extent with the former (29% vs 57%). This observation does not however, rule out a metabolic explanation. Cellular uptake of lipophilic xeno-biotics seems to involve simple partitioning of these compounds between the plasma lipoprotein and the cell membrane, without the need of a specific process involving cell receptors for LDL, and this has been demonstrated for benzo(a)-pyrene using LDL-receptor positive and negative cells; the cellular uptake of the carcinogen associated in vitro with LDL was similar for both cell lines (Remsen & Shireman, 1981). Although both observations on the mutagenicity and cytoxicity of lipopro-teins show that both activities are restricted to the VLDL fraction, it is not possible with the available data to conclude that a similar mechanism is responsible for these 2 phenomena. The fact that the study of Chan and Pollard has been carried out using pregnant rat lipoproteins, whereas ours uses human lipoproteins, is the main drawback in comparing the 2 activities. The …