title: Importance of phospholipids to nitrosourea interactions with the nuclear envelope and associated nucleic acids.
abstract: Nuclease digestion of triton isolated HeLa cell nuclei has resulted in nuclear envelopes containing less than 10% of the nuclear macromolecule. Alkylation and carbamoylation of the nuclear envelope (NE) fraction by chloroethylnitrosoureas (HNU) was disproportionately high (approximately 35% of total nuclear alkylation and approximately 55% carbamoylation) suggesting that the nucleophilic species in the envelope were preferential targets for drug binding. Digestion of the envelope fraction with phospholipase C (PLC), followed by buoyant density gradient separation in Percoll (70%):0.15 M NaCl (30%), demonstrated that some envelope:nucleic acid attachments were destabilized as a result of phospholipid cleavage. In addition, the buoyant density of HNU-modified NE macromolecules was slightly altered by PLC digestion, suggesting that cleavage of polar phospholipids did not completely destabilize the chloroethylated products from the nuclear envelope.
mesh_terms: D000478:Alkylation; D004247:DNA / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D009607:Nitrosourea Compounds / Q000494:pharmacology*; D009685:Nuclear Envelope / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism*; D012313:RNA / Q000378:metabolism*
chemical_list: D009607:Nitrosourea Compounds; D010743:Phospholipids; D012313:RNA; D004247:DNA