Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1981 Aug;78(8):5193–5196. doi: 10.1073/pnas.78.8.5193

Genetic variation in rates of antipyrine metabolite formation: a study in uninduced twins.

M B Penno, B H Dvorchik, E S Vesell
PMCID: PMC320370  PMID: 6946467

Abstract

Adult, male, unmedicated twins received antipyrine orally under carefully controlled environmental conditions. Relative contributions of genetic and environmental factors to 2-fold interindividual variations in rate constants for formation of the three main antipyrine metabolites were compared. Heritabilities for rate constants for formation of 4-hydroxyantipyrine, N-demethylantipyrine, and 3-hydroxymethylantipyrine were 0.88, 0.85, and 0.70, respectively. These results suggest that each molecular form of cytochrome P-450 that converts antipyrine to a different metabolite exhibits genetically controlled interindividual variations in activity. Unrelated adult male subjects whose environments were also carefully controlled exhibited highly reproducible rate constants for formation of antipyrine metabolites. Because the rate constant for metabolite formation sensitively detects certain variations in the gene product, it should be used in future pharmacogenetic studies on rates of production of multiple metabolites from a single parent drug.

Full text

PDF
5193

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alexanderson B., Evans D. A., Sjöqvist F. Steady-state plasma levels of nortriptyline in twins: influence of genetic factors and drug therapy. Br Med J. 1969 Dec 27;4(5686):764–768. doi: 10.1136/bmj.4.5686.764. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Andreasen P. B., Vesell E. S. Comparison of plasma levels of antipyrine, tolbutamide, and warfarin after oral and intravenous administration. Clin Pharmacol Ther. 1974 Dec;16(6):1059–1065. doi: 10.1002/cpt19741661059. [DOI] [PubMed] [Google Scholar]
  3. BRODIE B. B., AXELROD J. The fate of antipyrine in man. J Pharmacol Exp Ther. 1950 Jan;98(1):97–104. [PubMed] [Google Scholar]
  4. Banerji J., Rusconi S., Schaffner W. Expression of a beta-globin gene is enhanced by remote SV40 DNA sequences. Cell. 1981 Dec;27(2 Pt 1):299–308. doi: 10.1016/0092-8674(81)90413-x. [DOI] [PubMed] [Google Scholar]
  5. Bastos R. N., Aviv H. Globin RNA precursor molecules: biosynthesis and process in erythroid cells. Cell. 1977 Jul;11(3):641–650. doi: 10.1016/0092-8674(77)90081-2. [DOI] [PubMed] [Google Scholar]
  6. Baty J. D., Evans D. A. Norphenazone, a new metabolite of phenazone in human urine. J Pharm Pharmacol. 1973 Jan;25(1):83–84. doi: 10.1111/j.2042-7158.1973.tb09124.x. [DOI] [PubMed] [Google Scholar]
  7. Beltz G. A., Flint S. J. Inhibition of HeLa cell protein synthesis during adenovirus infection. Restriction of cellular messenger RNA sequences to the nucleus. J Mol Biol. 1979 Jun 25;131(2):353–373. doi: 10.1016/0022-2836(79)90081-0. [DOI] [PubMed] [Google Scholar]
  8. Berk A. J., Sharp P. A. Sizing and mapping of early adenovirus mRNAs by gel electrophoresis of S1 endonuclease-digested hybrids. Cell. 1977 Nov;12(3):721–732. doi: 10.1016/0092-8674(77)90272-0. [DOI] [PubMed] [Google Scholar]
  9. Bramwell M. E., Handmaker S. D. The effects of 'step-down on RNA' metabolism in Hela cells. Exp Cell Res. 1975 Mar 15;91(2):358–364. doi: 10.1016/0014-4827(75)90115-9. [DOI] [PubMed] [Google Scholar]
  10. Bramwell M. E., Harris H. The origin of the polydispersity in sedimentation patterns of rapidly labelled nuclear ribonucleic acid. Biochem J. 1967 Jun;103(3):816–830. doi: 10.1042/bj1030816. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Breathnach R., Chambon P. Organization and expression of eucaryotic split genes coding for proteins. Annu Rev Biochem. 1981;50:349–383. doi: 10.1146/annurev.bi.50.070181.002025. [DOI] [PubMed] [Google Scholar]
  12. Breathnach R., Mantei N., Chambon P. Corrected splicing of a chicken ovalbumin gene transcript in mouse L cells. Proc Natl Acad Sci U S A. 1980 Feb;77(2):740–744. doi: 10.1073/pnas.77.2.740. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Busslinger M., Moschonas N., Flavell R. A. Beta + thalassemia: aberrant splicing results from a single point mutation in an intron. Cell. 1981 Dec;27(2 Pt 1):289–298. doi: 10.1016/0092-8674(81)90412-8. [DOI] [PubMed] [Google Scholar]
  14. Carlson D. P., Ross J. Human beta-globin promoter and coding sequences transcribed by RNA polymerase III. Cell. 1983 Oct;34(3):857–864. doi: 10.1016/0092-8674(83)90543-3. [DOI] [PubMed] [Google Scholar]
  15. Cascorbi H. F., Vesell E. S., Blake D. A., Helrich M. Genetic and environmental influence on halothane metabolism in twins. Clin Pharmacol Ther. 1971 Jan-Feb;12(1):50–55. doi: 10.1002/cpt197112150. [DOI] [PubMed] [Google Scholar]
  16. Chan L. N. Transport of globin mRNA from nucleus into cytoplasm in differentiating embryonic red blood cells. Nature. 1976 May 13;261(5556):157–159. doi: 10.1038/261157a0. [DOI] [PubMed] [Google Scholar]
  17. Chao M. V., Mellon P., Charnay P., Maniatis T., Axel R. The regulated expression of beta-globin genes introduced into mouse erythroleukemia cells. Cell. 1983 Feb;32(2):483–493. doi: 10.1016/0092-8674(83)90468-3. [DOI] [PubMed] [Google Scholar]
  18. Chu G., Sharp P. A. A gene chimaera of SV40 and mouse beta-globin is transcribed and properly spliced. Nature. 1981 Jan 29;289(5796):378–382. doi: 10.1038/289378a0. [DOI] [PubMed] [Google Scholar]
  19. Chu G., Sharp P. A. SV40 DNA transfection of cells in suspension: analysis of efficiency of transcription and translation of T-antigen. Gene. 1981 Mar;13(2):197–202. doi: 10.1016/0378-1119(81)90008-1. [DOI] [PubMed] [Google Scholar]
  20. Collins M. L., Wu J. S., Santiago C. L., Hendrickson S. L., Johnson L. F. Delayed processing of dihydrofolate reductase heterogeneous nuclear RNA in amino acid-starved mouse fibroblasts. Mol Cell Biol. 1983 Oct;3(10):1792–1802. doi: 10.1128/mcb.3.10.1792. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Conney A. H., Pantuck E. J., Hsiao K. C., Kuntzman R., Alvares A. P., Kappas A. Regulation of drug metabolism in man by environmental chemicals and diet. Fed Proc. 1977 Apr;36(5):1647–1652. [PubMed] [Google Scholar]
  22. Cooper G. M. Cellular transforming genes. Science. 1982 Aug 27;217(4562):801–806. doi: 10.1126/science.6285471. [DOI] [PubMed] [Google Scholar]
  23. Corces V., Pellicer A., Axel R., Meselson M. Integration, transcription, and control of a Drosophila heat shock gene in mouse cells. Proc Natl Acad Sci U S A. 1981 Nov;78(11):7038–7042. doi: 10.1073/pnas.78.11.7038. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Crawford R. J., Wells J. R. Short half-life precursor of globin messenger RNA from chicken erythroblasts. Biochemistry. 1978 May 2;17(9):1591–1596. doi: 10.1021/bi00602a002. [DOI] [PubMed] [Google Scholar]
  25. Curtis P. J., Mantei N., van den Berg J., Weissmann C. Presence of a putative 15S precursor to beta-globin mRNA but not to alpha-globin mRNA in Friend cells. Proc Natl Acad Sci U S A. 1977 Aug;74(8):3184–3188. doi: 10.1073/pnas.74.8.3184. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Danhof M., Groot-van der Vis E., Breiner D. D. Assay of antipyrine and its primary metabolites in plasma, saliva and urine by high-performance liquid chromatography and some preliminary results in man. Pharmacology. 1979;18(4):210–223. doi: 10.1159/000137254. [DOI] [PubMed] [Google Scholar]
  27. Danhof M., Krom D. P., Breimer D. D. Studies on the different metabolic pathways of antipyrine in rats: influence of phenobarbital and 3-methylcholanthrene treatment. Xenobiotica. 1979 Nov;9(11):695–702. doi: 10.3109/00498257909042337. [DOI] [PubMed] [Google Scholar]
  28. De Robertis E. M., Lienhard S., Parisot R. F. Intracellular transport of microinjected 5S and small nuclear RNAs. Nature. 1982 Feb 18;295(5850):572–577. doi: 10.1038/295572a0. [DOI] [PubMed] [Google Scholar]
  29. Dierks P., van Ooyen A., Cochran M. D., Dobkin C., Reiser J., Weissmann C. Three regions upstream from the cap site are required for efficient and accurate transcription of the rabbit beta-globin gene in mouse 3T6 cells. Cell. 1983 Mar;32(3):695–706. doi: 10.1016/0092-8674(83)90055-7. [DOI] [PubMed] [Google Scholar]
  30. Dobkin C., Pergolizzi R. G., Bahre P., Bank A. Abnormal splice in a mutant human beta-globin gene not at the site of a mutation. Proc Natl Acad Sci U S A. 1983 Mar;80(5):1184–1188. doi: 10.1073/pnas.80.5.1184. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Doehmer J., Barinaga M., Vale W., Rosenfeld M. G., Verma I. M., Evans R. M. Introduction of rat growth hormone gene into mouse fibroblasts via a retroviral DNA vector: expression and regulation. Proc Natl Acad Sci U S A. 1982 Apr;79(7):2268–2272. doi: 10.1073/pnas.79.7.2268. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Duesberg P. H. Retroviral transforming genes in normal cells? Nature. 1983 Jul 21;304(5923):219–226. doi: 10.1038/304219a0. [DOI] [PubMed] [Google Scholar]
  33. Endrenyi L., Inaba T., Kalow W. Genetic study of amobarbital elimination based on its kinetics in twins. Clin Pharmacol Ther. 1976 Dec;20(6):701–714. doi: 10.1002/cpt1976206701. [DOI] [PubMed] [Google Scholar]
  34. Felber B. K., Orkin S. H., Hamer D. H. Abnormal RNA splicing causes one form of alpha thalassemia. Cell. 1982 Jul;29(3):895–902. doi: 10.1016/0092-8674(82)90451-2. [DOI] [PubMed] [Google Scholar]
  35. Fukumaki Y., Ghosh P. K., Benz E. J., Jr, Reddy V. B., Lebowitz P., Forget B. G., Weissman S. M. Abnormally spliced messenger RNA in erythroid cells from patients with beta+ thalassemia and monkey cells expressing a cloned beta+-thalassemic gene. Cell. 1982 Mar;28(3):585–593. doi: 10.1016/0092-8674(82)90213-6. [DOI] [PubMed] [Google Scholar]
  36. Ghosh P. K., Roy P., Barkan A., Mertz J. E., Weissman S. M., Lebowitz P. Unspliced functional late 19S mRNAs containing intervening sequences are produced by a late leader mutant of simian virus 40. Proc Natl Acad Sci U S A. 1981 Mar;78(3):1386–1390. doi: 10.1073/pnas.78.3.1386. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Gilmore-Hebert M., Wall R. Immunoglobulin light chain mRNA is processed from large nuclear RNA. Proc Natl Acad Sci U S A. 1978 Jan;75(1):342–345. doi: 10.1073/pnas.75.1.342. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Goldsmith M. E., Humphries R. K., Ley T., Cline A., Kantor J. A., Nienhuis A. W. "Silent" nucleotide substitution in a beta+-thalassemia globin gene activates splice site in coding sequence RNA. Proc Natl Acad Sci U S A. 1983 Apr;80(8):2318–2322. doi: 10.1073/pnas.80.8.2318. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Gruss P., Efstratiadis A., Karathanasis S., König M., Khoury G. Synthesis of stable unspliced mRNA from an intronless simian virus 40--rat preproinsulin gene recombinant. Proc Natl Acad Sci U S A. 1981 Oct;78(10):6091–6095. doi: 10.1073/pnas.78.10.6091. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Harpold M. M., Dobner P. R., Evans R., Bancroft F. C., Darnell J. E., Jr The synthesis and processing of a nuclear RNA precursor to rat pregrowth hormone messenger RNA. Nucleic Acids Res. 1979 Jul 11;6(9):3133–3144. doi: 10.1093/nar/6.9.3133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Huang A. L., Ostrowski M. C., Berard D., Hager G. L. Glucocorticoid regulation of the Ha-MuSV p21 gene conferred by sequences from mouse mammary tumor virus. Cell. 1981 Dec;27(2 Pt 1):245–255. doi: 10.1016/0092-8674(81)90408-6. [DOI] [PubMed] [Google Scholar]
  42. Humphries R. K., Ley T., Turner P., Moulton A. D., Nienhuis A. W. Differences in human alpha-, beta- and delta-globin gene expression in monkey kidney cells. Cell. 1982 Aug;30(1):173–183. doi: 10.1016/0092-8674(82)90023-x. [DOI] [PubMed] [Google Scholar]
  43. Inaba T., Fischer N. E. Antipyrine metabolism in man: simultaneous determination of norantipyrine and 4-hydroxyantipyrine in urine by gas chromatography. Can J Physiol Pharmacol. 1980 Jan;58(1):17–21. doi: 10.1139/y80-004. [DOI] [PubMed] [Google Scholar]
  44. Inaba T., Lucassen M., Kalow W. Antipyrine metabolism in the rat by three hepatic monooxygenases. Life Sci. 1980 Jun 9;26(23):1977–1983. doi: 10.1016/0024-3205(80)90629-3. [DOI] [PubMed] [Google Scholar]
  45. Jelinek W., Adesnik M., Salditt M., Sheiness D., Wall R., Molloy G., Philipson L., Darnell J. E. Further evidence on the nuclear origin and transfer to the cytoplasm of polyadenylic acid sequences in mammalian cell RNA. J Mol Biol. 1973 Apr 15;75(3):515–532. doi: 10.1016/0022-2836(73)90458-0. [DOI] [PubMed] [Google Scholar]
  46. Johnson L. F., Williams J. G., Abelson H. T., Green H., Penman S. Changes in RNA in relation to growth of the fibroblast. III. Posttranscriptional regulation of mRNA formation in resting and growing cells. Cell. 1975 Jan;4(1):69–75. doi: 10.1016/0092-8674(75)90135-x. [DOI] [PubMed] [Google Scholar]
  47. Kalow W., Kadar D., Inaba T., Tang B. K. A case of deficiency of N-hydroxylation of amobarbital. Clin Pharmacol Ther. 1977 May;21(5):530–535. doi: 10.1002/cpt1977215530. [DOI] [PubMed] [Google Scholar]
  48. Kinniburgh A. J., Maquat L. E., Schedl T., Rachmilewitz E., Ross J. mRNA-deficient beta o-thalassemia results from a single nucleotide deletion. Nucleic Acids Res. 1982 Sep 25;10(18):5421–5427. doi: 10.1093/nar/10.18.5421. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Klessig D. F., Chow L. T. Incomplete splicing and deficient accumulation of the fiber messenger RNA in monkey cells infected by human adenovirus type 2. J Mol Biol. 1980 May 15;139(2):221–242. doi: 10.1016/0022-2836(80)90306-x. [DOI] [PubMed] [Google Scholar]
  50. Kwan S. P., Wood T. G., Lingrel J. B. Purification of a putative precursor of globin messenger RNA from mouse nucleated erythroid cells. Proc Natl Acad Sci U S A. 1977 Jan;74(1):178–182. doi: 10.1073/pnas.74.1.178. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Lawn R. M., Efstratiadis A., O'Connell C., Maniatis T. The nucleotide sequence of the human beta-globin gene. Cell. 1980 Oct;21(3):647–651. doi: 10.1016/0092-8674(80)90428-6. [DOI] [PubMed] [Google Scholar]
  52. Lee F., Mulligan R., Berg P., Ringold G. Glucocorticoids regulate expression of dihydrofolate reductase cDNA in mouse mammary tumour virus chimaeric plasmids. Nature. 1981 Nov 19;294(5838):228–232. doi: 10.1038/294228a0. [DOI] [PubMed] [Google Scholar]
  53. Lewin B. Units of transcription and translation: sequence components of heterogeneous nuclear RNA and messenger RNA. Cell. 1975 Feb;4(2):77–93. doi: 10.1016/0092-8674(75)90113-0. [DOI] [PubMed] [Google Scholar]
  54. Lewin B. Units of transcription and translation: the relationship between heterogeneous nuclear RNA and messenger RNA. Cell. 1975 Jan;4(1):11–20. doi: 10.1016/0092-8674(75)90128-2. [DOI] [PubMed] [Google Scholar]
  55. Ley T. J., Nienhuis A. W. A weak upstream promoter gives rise to long human beta-globin RNA molecules. Biochem Biophys Res Commun. 1983 May 16;112(3):1041–1048. doi: 10.1016/0006-291x(83)91723-0. [DOI] [PubMed] [Google Scholar]
  56. Mangiarotti G., Zuker C., Chisholm R. L., Lodish H. F. Different mRNAs have different nuclear transit times in Dictyostelium discoideum aggregates. Mol Cell Biol. 1983 Aug;3(8):1511–1517. doi: 10.1128/mcb.3.8.1511. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Maquat L. E., Kinniburgh A. J., Rachmilewitz E. A., Ross J. Unstable beta-globin mRNA in mRNA-deficient beta o thalassemia. Cell. 1981 Dec;27(3 Pt 2):543–553. doi: 10.1016/0092-8674(81)90396-2. [DOI] [PubMed] [Google Scholar]
  58. Melton D. A., Cortese R. Transcription of cloned tRNA genes and the nuclear partitioning of a tRNA precursor. Cell. 1979 Dec;18(4):1165–1172. doi: 10.1016/0092-8674(79)90229-0. [DOI] [PubMed] [Google Scholar]
  59. Moschonas N., de Boer E., Grosveld F. G., Dahl H. H., Wright S., Shewmaker C. K., Flavell R. A. Structure and expression of a cloned beta o thalassaemic globin gene. Nucleic Acids Res. 1981 Sep 11;9(17):4391–4401. doi: 10.1093/nar/9.17.4391. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Orkin S. H., Sexton J. P., Cheng T. C., Goff S. C., Giardina P. J., Lee J. I., Kazazian H. H., Jr ATA box transcription mutation in beta-thalassemia. Nucleic Acids Res. 1983 Jul 25;11(14):4727–4734. doi: 10.1093/nar/11.14.4727. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Orkin S. H., Sexton J. P., Goff S. C., Kazazian H. H., Jr Inactivation of an acceptor RNA splice site by a short deletion in beta-thalassemia. J Biol Chem. 1983 Jun 25;258(12):7249–7251. [PubMed] [Google Scholar]
  62. Pelham H. R. A regulatory upstream promoter element in the Drosophila hsp 70 heat-shock gene. Cell. 1982 Sep;30(2):517–528. doi: 10.1016/0092-8674(82)90249-5. [DOI] [PubMed] [Google Scholar]
  63. Penman S., Vesco C., Penman M. Localization and kinetics of formation of nuclear heterodisperse RNA, cytoplasmic heterodisperse RNA and polyribosome-associated messenger RNA in HeLa cells. J Mol Biol. 1968 May 28;34(1):49–60. doi: 10.1016/0022-2836(68)90234-9. [DOI] [PubMed] [Google Scholar]
  64. Perry R. P., Kelley D. E., LaTorre J. Synthesis and turnover of nuclear and cytoplasmic polyadenylic acid in mouse L cells. J Mol Biol. 1974 Jan 25;82(3):315–331. doi: 10.1016/0022-2836(74)90593-2. [DOI] [PubMed] [Google Scholar]
  65. Poncz M., Schwartz E., Ballantine M., Surrey S. Nucleotide sequence analysis of the delta beta-globin gene region in humans. J Biol Chem. 1983 Oct 10;258(19):11599–11609. [PubMed] [Google Scholar]
  66. Prescott L. F., Adjepon-Yamoah K. K., Roberts E. Rapid gas-liquid chromatographic estimation of antipyrine in plasma. J Pharm Pharmacol. 1973 Mar;25(3):205–207. doi: 10.1111/j.2042-7158.1973.tb10625.x. [DOI] [PubMed] [Google Scholar]
  67. Raskas H. J. Release of adenovirus messenger RNA from isolated nuclei. Nat New Biol. 1971 Sep 29;233(39):134–136. doi: 10.1038/newbio233134a0. [DOI] [PubMed] [Google Scholar]
  68. Reddy V. B., Thimmappaya B., Dhar R., Subramanian K. N., Zain B. S., Pan J., Ghosh P. K., Celma M. L., Weissman S. M. The genome of simian virus 40. Science. 1978 May 5;200(4341):494–502. doi: 10.1126/science.205947. [DOI] [PubMed] [Google Scholar]
  69. Ross J. A precursor of globin messenger RNA. J Mol Biol. 1976 Sep 15;106(2):403–420. doi: 10.1016/0022-2836(76)90093-0. [DOI] [PubMed] [Google Scholar]
  70. Ross J., Pizarro A. Human beta and delta globin messenger RNAs turn over at different rates. J Mol Biol. 1983 Jul 5;167(3):607–617. doi: 10.1016/s0022-2836(83)80101-6. [DOI] [PubMed] [Google Scholar]
  71. Scherrer K., Marcaud L., Zajdela F., London I. M., Gros F. Patterns of RNA metabolism in a differentiated cell: a rapidly labeled, unstable 60S RNA with messenger properties in duck erythroblasts. Proc Natl Acad Sci U S A. 1966 Nov;56(5):1571–1578. doi: 10.1073/pnas.56.5.1571. [DOI] [PMC free article] [PubMed] [Google Scholar]
  72. Schlosser C. A., Steglich C., deWet J. R., Scheffler I. E. Cell cycle-dependent regulation of thymidine kinase activity introduced into mouse LMTK- cells by DNA and chromatin-mediated gene transfer. Proc Natl Acad Sci U S A. 1981 Feb;78(2):1119–1123. doi: 10.1073/pnas.78.2.1119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  73. Schodhetman G., Perry R. P. Early appearance of histone messenger RNA in polyribosomes of cultured L cells. J Mol Biol. 1972 Feb 14;63(3):591–596. doi: 10.1016/0022-2836(72)90450-0. [DOI] [PubMed] [Google Scholar]
  74. Singer R. H., Penman S. Messenger RNA in HeLa cells: kinetics of formation and decay. J Mol Biol. 1973 Aug 5;78(2):321–334. doi: 10.1016/0022-2836(73)90119-8. [DOI] [PubMed] [Google Scholar]
  75. Stuart S. E., Rottman F. M., Patterson R. J. Nuclear restriction of nucleic acids in the presence of ATP. Biochem Biophys Res Commun. 1975 Jan 20;62(2):439–447. doi: 10.1016/s0006-291x(75)80158-6. [DOI] [PubMed] [Google Scholar]
  76. Sutcliffe J. G. Complete nucleotide sequence of the Escherichia coli plasmid pBR322. Cold Spring Harb Symp Quant Biol. 1979;43(Pt 1):77–90. doi: 10.1101/sqb.1979.043.01.013. [DOI] [PubMed] [Google Scholar]
  77. Therwath A., Scherrer K. Post-transcriptional suppression of globin gene expression in cells transformed by avian erythroblastosis virus. Proc Natl Acad Sci U S A. 1978 Aug;75(8):3776–3780. doi: 10.1073/pnas.75.8.3776. [DOI] [PMC free article] [PubMed] [Google Scholar]
  78. Treisman R., Green M. R., Maniatis T. cis and trans activation of globin gene transcription in transient assays. Proc Natl Acad Sci U S A. 1983 Dec;80(24):7428–7432. doi: 10.1073/pnas.80.24.7428. [DOI] [PMC free article] [PubMed] [Google Scholar]
  79. Treisman R., Orkin S. H., Maniatis T. Specific transcription and RNA splicing defects in five cloned beta-thalassaemia genes. Nature. 1983 Apr 14;302(5909):591–596. doi: 10.1038/302591a0. [DOI] [PubMed] [Google Scholar]
  80. Treisman R., Proudfoot N. J., Shander M., Maniatis T. A single-base change at a splice site in a beta 0-thalassemic gene causes abnormal RNA splicing. Cell. 1982 Jul;29(3):903–911. doi: 10.1016/0092-8674(82)90452-4. [DOI] [PubMed] [Google Scholar]
  81. Vesell E. S., Page J. G. Genetic control of drug levels in man: antipyrine. Science. 1968 Jul 5;161(3836):72–73. doi: 10.1126/science.161.3836.72. [DOI] [PubMed] [Google Scholar]
  82. Vesell E. S., Page J. G. Genetic control of the phenobarbital-induced shortening of plasma antipyrine half-lives in man. J Clin Invest. 1969 Dec;48(12):2202–2209. doi: 10.1172/JCI106186. [DOI] [PMC free article] [PubMed] [Google Scholar]
  83. Vesell E. S., Passananti G. T., Glenwright P. A., Dvorchik B. H. Studies on the disposition of antipyrine, aminopyrine, and phenacetin using plasma, saliva, and urine. Clin Pharmacol Ther. 1975 Sep;18(3):259–272. doi: 10.1002/cpt1975183259. [DOI] [PubMed] [Google Scholar]
  84. Vesell E. S. The antipyrine test in clinical pharmacology: conceptions and misconceptions. Clin Pharmacol Ther. 1979 Sep;26(3):275–286. doi: 10.1002/cpt1979263275. [DOI] [PubMed] [Google Scholar]
  85. Vesell E. S. Twin studies in pharmacogenetics. Hum Genet Suppl. 1978;(1):19–30. doi: 10.1007/978-3-642-67179-1_4. [DOI] [PubMed] [Google Scholar]
  86. Warner J. R., Soeiro R., Birnboim H. C., Girard M., Darnell J. E. Rapidly labeled HeLa cell nuclear RNA. I. Identification by zone sedimentation of a heterogeneous fraction separate from ribosomal precursor RNA. J Mol Biol. 1966 Aug;19(2):349–361. doi: 10.1016/s0022-2836(66)80009-8. [DOI] [PubMed] [Google Scholar]
  87. Weaver R. F., Weissmann C. Mapping of RNA by a modification of the Berk-Sharp procedure: the 5' termini of 15 S beta-globin mRNA precursor and mature 10 s beta-globin mRNA have identical map coordinates. Nucleic Acids Res. 1979 Nov 10;7(5):1175–1193. doi: 10.1093/nar/7.5.1175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  88. Whitelaw E., Proudfoot N. J. Transcriptional activity of the human pseudogene psi alpha globin compared with alpha globin, its functional gene counterpart. Nucleic Acids Res. 1983 Nov 25;11(22):7717–7733. doi: 10.1093/nar/11.22.7717. [DOI] [PMC free article] [PubMed] [Google Scholar]
  89. Wickens M. P., Gurdon J. B. Post-transcriptional processing of simian virus 40 late transcripts in injected frog oocytes. J Mol Biol. 1983 Jan 5;163(1):1–26. doi: 10.1016/0022-2836(83)90027-x. [DOI] [PubMed] [Google Scholar]
  90. Wold B., Wigler M., Lacy E., Maniatis T., Silverstein S., Axel R. Introduction and expression of a rabbit beta-globin gene in mouse fibroblasts. Proc Natl Acad Sci U S A. 1979 Nov;76(11):5684–5688. doi: 10.1073/pnas.76.11.5684. [DOI] [PMC free article] [PubMed] [Google Scholar]
  91. Yoshimura H., Shimeno H., Tsukamoto H. Metabolism of drugs. LIX. A new metabolite of antipyrine. Biochem Pharmacol. 1968 Aug;17(8):1511–1516. doi: 10.1016/0006-2952(68)90210-4. [DOI] [PubMed] [Google Scholar]
  92. Zasloff M., Rosenberg M., Santos T. Impaired nuclear transport of a human variant tRNAiMet. Nature. 1982 Nov 4;300(5887):81–84. doi: 10.1038/300081a0. [DOI] [PubMed] [Google Scholar]
  93. Zasloff M. tRNA transport from the nucleus in a eukaryotic cell: carrier-mediated translocation process. Proc Natl Acad Sci U S A. 1983 Nov;80(21):6436–6440. doi: 10.1073/pnas.80.21.6436. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES