desmosterol and Neurilemmoma

Desmosterol, a possible chemical indicator of brain tumors, was detected in cells of neurogenic, nitrosourea-induced rat tumors (neurinomas and gliomas, C6 cell line) and in human astrocytomas grown in lipid-poor media. A further increase in the amount of cell desmosterol was obtained when triparanol was added to media containing delipidized serum. Cholesterol was replaced almost completely by desmosterol in tumor cells grown in media containing nontoxic levels of 20,25-diazacholesterol. Desmosterol did not accumulate when these inhibitors of desmosterol-reductase were added to culture media containing cholesterol and other lipids (whole fetal calf serum). The results demonstrate that tumors of the nervous system grown in tissue culture are capable of sterol synthesis, and indicate that a central mechanism of cholesterol synthesis is operative in these cells, which may be related to the availability of exogenous cholesterol. It is concluded that these findings are relevant to clinical studies on the use of cholesterol inhibitors as tools for the detection of brain tumor activity.

Topics: Animals; Astrocytoma; Brain Neoplasms; Cells, Cultured; Cholesterol; Desmosterol; Fibroblasts; Glioma; Humans; L Cells; Neoplasms, Experimental; Neurilemmoma; Rats

Desmosterol (5, 24-cholestadien-3beta-ol; delta 24-cholesterol; 24-dehydrocholesterol), an immediate precursor of brain cholesterol, increased in malignant intracranial tumors induced in rats by nitrosourea derivatives. The average increase in desmosterol was higher in intracerebral gliomas than in neurinomas of the trigeminal nerve. Similarly, desmosterol increased only slightly in developing normal trigeminal nerve compared to the high levels observed in developing cerebrum. The differences may have been partly related to the predominantly growing cell type, i.e., glial (central nervous system) or Schwann (peripheral nervous system) cells seen at the time of study.

Topics: Age Factors; Animals; Brain Neoplasms; Carcinogens; Cholesterol; Desmosterol; Female; Fetal Diseases; Gestational Age; Glioma; Neoplasms, Experimental; Neurilemmoma; Nitrosourea Compounds; Peripheral Nervous System Neoplasms; Pregnancy; Rats; Rats, Inbred Strains; Trigeminal Nerve

The composition and distribution of steryl esters in human diseased or developing brain tissue has been studied. The abnormal brain conditions included sudanophilic leukodystrophy, multiple sclerosis plaque, subacute sclerosing panencephalitis, and an old cerebral infarction and two types of brain-derived tumors. In addition to the above abnormal tissue, steryl esters were also examined in developing and normal adult human brain. It was found upon subcellular fractionation that the steryl ester was localized mainly in the soluble nonparticulate material. A cholesteryl ester-rich fraction, floating on top of distilled water after centrifugation, was recovered only in the developing brain or in instances where there was myelin damage. The sterol portion of the steryl ester was largely cholesterol. The fatty acid moiety was mainly composed of C(16), C(18), and C(20) fatty acids. The dominant fatty acid was oleic acid, and the proportion of this fatty acid increased in demyelination. Although there were great differences in the quantities of steryl ester found, the fatty acid profiles of normal developing and adult brain were quite similar. As has been noted by others, the fatty acid composition of brain steryl esters most closely resembles that of brain phosphatidylcholine.

Topics: Adult; Brain; Brain Neoplasms; Cholesterol; Chromatography; Chromatography, Gas; Corpus Callosum; Desmosterol; Esters; Fatty Acids; Humans; Infant; Infant, Newborn; Infarction; Lanosterol; Leukodystrophy, Metachromatic; Multiple Sclerosis; Neurilemmoma; Oligodendroglioma; Silicon Dioxide; Sterols; Subacute Sclerosing Panencephalitis; Subcellular Fractions

Topics: Animals; Brain; Brain Neoplasms; Desmosterol; DNA; DNA, Neoplasm; Ependymoma; Female; Glioma; Neurilemmoma; Nitrosourea Compounds; Oligodendroglioma; Rats; RNA; RNA, Neoplasm; Sarcoma; Spinal Cord Neoplasms; Thymidine