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Walter Reed Army Medical Center, Washington, D.C. 20012, and University of Connecticut School of Medicine, Hartford, Connecticut 06112
Administration of nickel carbonyl to rats inhibited RNA synthesis by a chromatin-RNA polymerase complex prepared from lysed hepatic nuclei. Rats were killed 6 hr after i.v. administration of Ni(CO)4 in LD50 dosage (2.2 mg Ni/100 g body weight). The rate of RNA synthesis by the chromatin-RNA polymerase complex from Ni(CO)4-treated rats averaged 0.16 (S.E. = ±0.02, N = 18) µmole cytidine triphosphate-3H/10 min/g DNA (controls = 0.33 ± 0.03, N = 18, p < 0.001). The molar ratio of Ni to DNA nucleotides in the chromatin-RNA polymerase complex from Ni(CO)4-treated rats averaged 0.046, and the concentration of nickel in the final assay mixtures averaged 3.4 x 10-6 M. In vitro additions of Ni(CO)4 or NiCl2 in final concentrations of 1 x 10-5 M to assay mixtures containing chromatin-RNA polymerase complex from control rats did not inhibit the incorporation of cytidine triphosphate-3H into RNA. This study shows that in vivo administration of Ni(CO)4 to rats produces inhibition of RNA synthesis which persists after disruption of hepatic nuclei and excludes inhibition owing to impaired transport of RNA precursors across the nuclear membrane.
1 This investigation was supported by U. S. Atomic Energy Commission Grant AT(30-1)4051, American Cancer Society Grant E-374C, and USPHS Research Grant CA 11250-01 from the National Cancer Institute.
Received 4/ 1/69. Accepted 5/ 7/69.
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