[' ', '1.', '120-136', 'hours.', 'The', 'most', 'populated', 'cultures', 'containing', 'the', 'sterol,', 'however,', 'revealed', 'no', 'inhibition', 'of', 'DNA', 'synthesis', 'at', '120-136', 'hours', 'when', 'compared.', 'to', 'controls.', 'Similar', 'results', 'were', 'found', '.using.', '200', 'hydroxycholesterol.', '_', 'We', 'next', 'studied', 'the', 'effect', 'of', 'OSC', 'upon', 'the', 'ability', 'of', '.control', 'and', 'mitogen-', 'stimulated.', 'lymphocyté.', 'cultures', 'to', 'synthesize', 'sterols', 'from', 'radioactive', 'acetate', 'precursor.', 'Resting', 'lymphocytes', 'increase', 'their', 'rate.of', 'sterol', 'synthesis', 'approxi-', 'mately', 'four-fold', 'during', 'a.17-hour', 'incubation', 'in', 'medium', 'supplemented', 'with', 'LPDS.', 'Therefore,', 'the', 'rate', 'of', 'sterol', 'synthesis.', 'in', 'mitogen-stimulated.', 'lymphocytes.', 'which', 'had', 'been', 'incubated', 'in', 'LPDS', 'was', 'compared', 'with', 'that.', 'for', 'the.same', 'cells', 'incubated', 'in.', 'cholesterol-containing', 'media.', 'Since', 'the', 'level', 'of', 'sterol', 'synthesis', 'in', 'Con', 'A-', 'stimulated', 'lymphocytes', 'in', 'LPDS', 'medium', 'was', '2', 'to', '5', 'times', 'that', 'in', 'cholesterol-', 'containing', 'cultures,', 'most.', 'of', 'our', 'sterol-synthetic', 'studies', 'were', 'performed', 'in.', 'cholesterol-depleted', '.LPDS.', 'medium.', 'Both', '25', 'hydroxycholesterol', 'and', '20a', 'hydroxycholesterol', 'inhibited.', 'lymphocyte', '.', 'sterol', 'synthesis', 'almost', 'completely', 'in', 'resting', 'and', 'mitogen-stimulated', 'cultures', 'at', 'concentrations', 'of', '2.5.x10-5M', 'and', '2.5.x', '10-6M.in', 'the', 'case', 'of', '25', 'hydroxychole-', 'sterols', 'this', 'degree', 'of', 'inhibition', 'of', 'sterol', 'synthesis.', 'exceeded', 'the.', 'capacity', 'of', 'these', 'sterols', 'to', 'inhibit', 'DNA', 'synthesis', 'in', 'lymphocyte', 'cultures', 'when', 'the', 'latter', 'was', 'measured,', 'as.shown', 'earlier,.in', 'cultures', 'performed-in.the', 'presence', 'of', '12.5%', 'normal', 'serum', 'containing', 'lipoprotein', 'and.', 'cholesterol.', '—', 'Other', 'matamalian', 'cells,.whose', 'replication', 'in', 'tissue.culture', 'is', 'blocked', 'by', 'inhibition', '.of', 'sterol-synthesis,', 'can', 'be', 'restored', 'to.growth', 'if.', 'the', 'cells', 'are', 'pro-', 'vided', 'with', 'mevalonic', 'acid,', 'a', 'precursor.', 'of', 'cholesterol', 'which', 'bypasses', 'the', 'need', 'for', 'the', 'enzyme', 'HMG-CoA', 'reductase.', 'Therefore,', 'we', 'tested', 'the', 'capacity.of', 'this.', 'compound', 'to', 'overcome', 'the', 'inhibition.', 'of', 'lymphocyte', 'DNA', 'synthesis', 'caused', 'by', '25', 'hydroxy-', 'cholesterol.', 'These', 'experiments', 'reveal', 'that', 'mevalonic', 'acid', '(a)', 'increases', 'the', 'amount', 'of', 'DNA', 'synthesis', 'in', 'resting', 'lymphocytes;', '(b)', 'slightly', 'diminishes', 'the', 'amount', 'of', 'DNA.synthesized', 'by', 'Con', 'A', 'stimulated', 'lymphocytes;', 'and', '(c}', 'allows', 'Con', 'A-', 'stimulated.', 'lymphocytes', 'to', 'overcome', 'the', 'inhibition', 'of', 'DNA', 'synthesis', 'imposed', 'by', 'the', 'sterol', 'to', 'a', 'slight,', 'but', 'significant', 'extent', 'in', 'medium', 'supplemented', 'with', 'normal', 'serum;', 'reversal', 'of', 'DNA', 'synthesis', 'inhibition', 'by', 'mevalonate', 'is', 'greatly', 'enhanced', 'by', 'the', 'use', 'of', 'LPDS-containing', 'medium.', 'When', 'resting', 'or', 'initogen-stimulated', 'human.', 'lymphocytes', 'are', 'cultured', 'in', 'the', 'pre-', 'sence', 'of', '25', 'hydroxycholesterol,', 'sterol', 'synthesis', 'from', '14c-acetate.', 'precursor', 'can', 'be', 'totally', 'suppressed', 'at', '18-24', 'hours', '-in', 'lipoprotein', '(and', 'cholesterol', ')-contain-', 'ing', 'as', 'well.', 'as', 'in', 'lipoprotein-depleted', 'medium.', 'In.each', 'case,', 'the', '50%.', 'inhibitory', 'dose', '(IHDsq)', 'is', 'the', 'same', '(#2.7', 'x', '10-7M).', 'On', 'the', 'other', 'hand,', 'lymphocyte', 'DNA', 'synthesis', 'as', 'measured', 'by', '14C-thymidine', 'incorporation.', 'into', 'DNA', 'is', 'normal', 'when', 'assayed', 'at', '24-40', 'hours', 'following', 'mitogen', 'stimulation.', '.', 'Suppression', 'of', 'DNA', 'synthesis', 'is', 'marked,', 'however,', '72-88.', 'hours', 'following', 'culture', 'initiation.', '.', 'Inhibi-', 'tion', 'of', 'DNA', 'synthesis', 'requires', 'a', 'concentration', 'of', '25.', 'hydroxycholesterol', 'which', 'is', 'an', 'order', 'of', 'magnitude', 'greater', 'in', 'lipoprotein-containing', 'medium', '(THD5g', '=', '4.3', '+', '1.1', 'x', '10°6M)', 'than', 'in', 'LPDM', '(IHD5q', '=', '3.9', '+', '2.5', 'x', '10-7M).', 'The.', 'IHDg9.', 'of.', '7a.', 'hydroxy-', 'cholesterol.', 'for', 'inhibition', 'of', 'lymphocyte', 'DNA.', 'synthesis.', 'changes', 'in', 'an', 'analogous', 'manner.', 'Similar', 'effects', 'on', 'the', 'IHD5q', 'for', 'inhibition', 'of.mitogen-stimulated', 'lymphocyte', 'DNA', 'synthesis', 'by', 'OSC', 'can', 'be', 'seen.with', 'the', 'addition.to', 'LPDM', 'of', '150', 'ug', 'protein/ml', 'total', 'human', 'lipoprotein', '(density', '<1.21),', '50-100', 'ug/ml', 'free', 'cholesterol,', '50', 'ug', 'protein/ml', 'low-density', 'human', 'serum', 'lipoprotein,', 'and', 'very', 'low-density', 'human', 'serum', 'lipoprotein,', 'but', 'not', 'with', 'high-density', 'human', 'serum', 'lipoprotein', '(up', 'to', '50147281']