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Nuclear Envelope Alterations Accompanying Thioacetamide-related Enlargement of the Nucleus¹

Department of Pathology, University of California School of Medicine, San Francisco, California 94143

Treating rats with thioacetamide results in a biphasic nuclear swelling, with an initial enlargement phase (0 to 8 hr) and a secondary phase (18 to 48 hr). The swelling coincides with and may be responsible for alterations in sedimentation properties of isolated nuclei. Nuclear swelling implies increases in nuclear surface area. Total nuclear lipid increased in proportion to the increase in nuclear-envelope (NE) surface area, suggesting that intranuclear lipid was not the source of new NE phospholipid. The increased NE was apparently not derived from mass incorporation of endoplasmic reticulum into NE, as demonstrated by monitoring enzymatic composition. Significant differences were observed in the distribution of p.o. administered [¹⁴C]stearic acid and [¹⁴C]phosphatidylcholine in lipid fractions from NE as compared with those from endoplasmic reticulum. Analysis of NE phospholipid revealed little change in composition in the heavy fraction during the first 48 hr after treatment. (An early decrease in phosphatidylserine from the light nuclear fraction may reflect the upward shift of nuclei from the heavy fraction.) A significant increase in phosphatidylserine of NE from the heavy fraction was found at 96 hr. The additional phosphatidylserine in the NE might act as an acidic polymer modifying chromatin structure. Examination of fatty acids from individual NE phospholipid fractions divulged relatively few changes related to the early or the secondary nuclear swelling phases. Major changes occurred in the neutral lipid fraction of NE which apparently served as a reservoir for 18:2, with significant decreases in 18:2 noted following both nuclear swelling phases. These changes did not occur in the neutral lipid fraction from endoplasmic reticulum obtained from the same liver preparations.

¹ This investigation was supported by USPHS Grants CA21141 and AM19843 and a Monsanto Fund Fellowship.

² To whom requests for reprints should be addressed.

Received 4/ 1/80. Accepted 10/31/80.