Plasma and cellular markers of 3′-azido-3′-dideoxythymidine (AZT) metabolism as indicators of DNA damage in cord blood mononuclear cells from infants receiving prepartum NRTIs

Environmental and Molecular Mutagenesis

Volumn 48, Issue 3-4, 2007, Pages 307-321

  Meng, Quanxin ^a,b,c   Olivero, Ofelia A ^d   Fasco, Michael J ^a,b   Bellisario, Ronald ^a   Kaminsky, Laurence ^a,b   Pass, Ken A ^a,b   Wade, Nancy A ^e   Abrams, Elaine J ^f   Nesel, Carol J ^g   Ness, Roberta B ^h   Bigbee, William L ^h,i   O'Neill, J Patrick ^j   Walker, Dale M ^a,c,k   Poirier, Miriam C ^d   Walker, Vernon E ^a,b,c,k  

^a WADSWORTH CENTER   (United States)

^b STATE UNIVERSITY OF NEW YORK   (United States)

^c LOVELACE RESPIRATORY RESEARCH INSTITUTE   (United States)

^d NATIONAL CANCER INSTITUTE   (United States)

^e ALBANY MEDICAL CENTER   (United States)

^f Harlem Hospital Center ^*  (United States)

^g WESTAT   (United States)

^h UNIVERSITY OF PITTSBURGH GRADUATE SCHOOL OF PUBLIC HEALTH   (United States)

ⁱ UNIVERSITY OF PITTSBURGH   (United States)

^j UNIVERSITY OF VERMONT   (United States)

^k UNIVERSITY OF NEW MEXICO   (United States)

more..

Author keywords

3TC DNA incorporation; AZT DNA incorporation; Lamivudine; Transplacental genotoxicity; Zidovudine

Indexed keywords

CELL MARKER; CELL NUCLEUS DNA; DRUG METABOLITE; LAMIVUDINE; NUCLEOSIDE ANALOG; RNA DIRECTED DNA POLYMERASE INHIBITOR; UNCLASSIFIED DRUG; ZIDOVUDINE; ZIDOVUDINE 5' DIPHOSPHATE; ZIDOVUDINE 5' PHOSPHATE; ZIDOVUDINE 5' TRIPHOSPHATE; ZIDOVUDINE GLUCURONIDE;

ARTICLE; CARCINOGEN DNA INTERACTION; CHEMICAL MUTAGENESIS; DNA DAMAGE; DRUG BLOOD LEVEL; DRUG METABOLISM; FEMALE; GENOTOXICITY; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; INFANT; MAJOR CLINICAL STUDY; MONONUCLEAR CELL; NEWBORN; PERINATAL DRUG EXPOSURE; PLACENTAL TRANSFER; RADIOIMMUNOASSAY; SOMATIC MUTATION; UMBILICAL CORD BLOOD;

ANTI-HIV AGENTS; BIOLOGICAL MARKERS; DNA; DNA DAMAGE; FEMALE; FETAL BLOOD; HIV INFECTIONS; HUMANS; INFANT, NEWBORN; LAMIVUDINE; LEUKOCYTES, MONONUCLEAR; MATERNAL-FETAL EXCHANGE; PREGNANCY; PREGNANCY COMPLICATIONS, INFECTIOUS; REVERSE TRANSCRIPTASE INHIBITORS; ZIDOVUDINE;

HUMAN IMMUNODEFICIENCY VIRUS 1;

EID: 34047196474     PISSN: 08936692     EISSN: 10982280     Source Type: Journal    
DOI: 10.1002/em.20298     Document Type: Article

References (64)

1. Acosta EP, Page LM, Fletcher CV. 1996. Clinical pharmacokinetics of zidovudine: An update. Clin Pharmacokinet 30:251-262.
2. Agarwal RP, Olivero OA. 1997. Genotoxicity and mitochondrial damage in human lymphocytic cells chronically exposed to 3′-azido-2′,3′- dideoxythymidine. Mutat Res 390:223-231.
3. Avramis VI, Markson W, Jackson RL, Gomperts E. 1989. Biochemical pharmacology of zidovudine in human T-lymphoblastoid cells (CEM). AIDS 3:417-422.
4. Ayers KM, Clive D, Tucker WE, Jr Hajian G, Miranda P. 1996. Non-clinical toxicology studies with zidovudine: Genetic tests and carcinogenicity bioassays in mice and rats. Fundam Appl Toxicol 32:148-158.
5. Balzarini J, Herdewijn P, De Clercq E. 1989. Differential patterns of intracellular metabolism of 2′, 3′-didehydro-2′, 3′-dideoxythymidine (d4T) and 3(-azido-2′, 3-dideoxythymidine (AZT), two potent anti-HIV compounds. J Biol Chem 264:6127-6133.
6. Barry M, Wild M, Veal G, Back D, Breckenridge A, Fox R, Beeching N, Nye F, Carey P, Timmins D. 1994. Zidovudine phosphorylation in HIV-infected patients and seronegative volunteers. AIDS 8:F1-F5.
7. Bhana N, Ormrod D, Perry CM, Figgitt DP. 2002. Zidovudine: A review of its use in the management of vertically-acquired pediatric HIV infection. Paediatr Drugs 4:515-553.
8. Collier A, Bozzette S, Coombs R, Causey D, Schoenfeld D, Spector S, Pettinelli C, Davies G, Richman D, Leedom J, Kidd P, Correy L. 1990. A pilot study of low-dose zidovudine in human immunodeficiency virus infection [see comments]. N Engl J Med 323:1015-1021.
9. Connor EM, Sperling RS, Gelber R, Kiselev P, Scott G, O'Sullivan MJ, Van Dyke R, Bey M, Shearer W, Jacobson RL, Jimenez E, O'Neill E, Bazin B, Delfraissy J-F, Culane M, Coombs R, Elkins M, Moye J, Stratton P, Balsley J. 1994. Reduction of maternal-infant transmission of human immunodeficiency virus type I with zidovudine treatment. N Engl J Med 331:1173-1180.
10. Diwan BA, Riggs CW, Logsdon D, Haines DC, Olivero OA, Rice JM, Yuspa SH, Poirier MC, Anderson LM. 1999. Multiorgan transplacental and neonatal carcinogenicity of 3′-azido-2′,3′-dideoxythymidine in mice. Toxicol Appl Pharmacol 161:82-99.
11. Eagling VA, Howe JL, Barry MJ, Back DJ. 1994. The metabolism of zidovudine by human liver microsomes in vitro: Formation of 3′-amino-3±-deoxythymidine. Biochem Pharmacol 48:267-276.
12. Escobar P, Olivero OA, Wade NA, Abrams EJ, Nesel CJ, Ness RB, Day RD, Day BW, Meng Q, O'Neill JP, Walker DM, Poirier MC, Walker VE, Bigbee WL, for the Study Team. 2007. Genotoxicity assessed by the Comet and GPA assays following in vitro exposure of human lymphoblastoid cells (H9) or perinatal exposure of mother-child pairs to AZT or AZT-3TC. Environ Mol Mutagen 48:330-343.
13. Finette BA, Sullivan LM, O'Neill JP, Nicklas JA, Vacek PM, Albertini RJ. 1994. Determination of hprt mutant frequencies in T-lymphocytes from a healthy pediatric population: Statistical comparison between newborn, children and adult mutant frequencies, cloning efficiency and age. Mutat Res 308:223-231.
14. Finette BA, O'Neill JP, Vacek PM, Albertini RJ. 1998. Gene mutations with characteristic deletions in cord blood T lymphocytes with passive maternal exposure to tobacco smoke. Nat Med 4:1144-1151.
15. Fischl MA, Parker CB, Pettinelli C, Wulfsohn M, Hirsch MS, Collier AC, Antoniskis D, Ho M, Richman DD, Fuchs E. 1990. A randomized controlled trial of a reduced daily dose of zidovudine in patients with acquired immunodeficiency syndrome. N Engl J Med 323:1009-1014.
16. Fletcher CV, Acosta EP, Henry K, Page LM, Gross CR, Kawle SP, Remmel RP, Erice A, Balfour HH Jr. 1998. Concentration-controlled zidovudine therapy. Clin Pharmacol Ther 64:331-338.
17. Fletcher CV, Kawle SP, Kakuda TN, Anderson PL, Weller D, Bushman LR, Brundage RC, Remmel RP. 2000. Zidovudine triphosphate and lamivudine triphosphate concentration-response relationships in HIV-infected persons. AIDS 14:2137-2144.
18. Furman PA, Fyfe JA, Clair MH St, Weinhold K, Rideout JL, Freeman GA, Lehrman SN, Bolognesi DP, Broder S, Mitsuya H, Barry DW. 1986. Phosphorylation of 3′-azido-3′-deoxythymidine and selective interaction of the 5′triphosphate with human immunoefticiency virus reverse transcriptase. Proc Natl Acad Sci USA 83:8333-8337.
19. Gomez DE, Kassim A, Olivero OA. 1995. Preferential incorporation of 3′-azido-3±-deoxythymidine (AZT) in telomeric sequences of CHO cells. Int J Oncol 7:1057-1060.
20. Hoogard PG, Sales SD, Kewn S, Sunderland D, Khoo SH, Hart CA, Back DJ. 2000. Correlation between intracellular pharmacological activation of nucleoside analogues and HIV suppression in vitro. Antivir Chem Chemother 11:353:358
21. International Agency for Research on Cancer (IARC). 2000. General remarks, and the monograph on zidovudine. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Some Antiviral and Antineoplastic Drugs, and Other Pharmaceutical Agents. Lyon:IARC. pp 35-42;73-127. IARC Scientific Publication No. 76.
22. Kuster H, Vogt M, Joos B, Nadai V, Luthy R. 1991. A method for the quantification of intracellular zidovudine nucleosides. J Infect Dis 164:773-776.
23. Lavie A, Schlichting I, Vetter IR, Konrad M, Reinstein J, Goody RS. 1997. The bottleneck of AZT activation. Nat Med 3:922-924.
24. McGinniss MJ, Falta MT, Sullivan LS, Albertini RJ. 1990. In vivo mutant frequencies in T-cells of normal newborns. Mutat Res 240:117-126.
25. Meng Q, Su T, Olivero OA, Poirier MC, Shi X, Ding X, Walker VE. 200Oa. Relationship between DNA incorporation, mutant frequency, and loss of heterozygosity at the TK locus in human lymphoblastoid cells exposed to 3′-azido-3′-deoxythymidine. Toxicol Sci 54:322-329.
26. Meng Q, Grosovsky AJ, Shi X, Walker VE. 2000b. Mutagenicity and loss of heterozygosity at the APRT locus in human lymphoblastoid cells exposed to 3′-azido-3′-deoxythymidine. Mutagen 15:405-410.
27. Meng Q, Walker DL, Olivero OA, Shi X, Antiochos BB, Poirier MC, Walker VE. 200Oc. AZT-ddI coexposure potentiates DNA incorporation of AZT, mutagenesis in human cells. Proc Natl Acad Sci USA 97:12667-12671.
28. Mofenson LM. 2004. Successes and challenges in the perinatal HIV-1 epidemic in the United States as illustrated by the HIV-1 serosurvey of child-bearing women. Arch Pediatr Adolesc Med 158:422-425.
29. Nicolas F, de Sousa D, Thomas P, Placidi M, Lorenzon G, Rahmani R. 1995. Comparative metabolism of 3′-azido-3′-deoxythymidine in cultured hepatocytes from rats, dogs, monkeys, and humans. Drug Metab Dispos 23:308-313.
30. National Toxicology Program (NTP). 2006. Toxicology and carcinogenesis of transplacental AZT (CAS No. 30516-87-1) in Swiss (CD-1) mice (in utero studies). US Department of Health and Human Services: Research Triangle Park.
31. Olivero OA, Beland FA, Fullerton NF, Poirier MC. 1994a. Vaginal epithelial DNA damage and expression of preneoplastic markers in mice during chronic dosing with tumorigenic levels of 3′-azido-2′,3′- dideoxythymidine. Cancer Res 54:6235-6242.
32. Olivero OA, Beland FA, Poirier MC. 1994b. Immunofluorescent localization and quantitation of 3′-azido-2′,3′-dideoxythymidine (AZT) incorporated into chromosomal DNA of human, hamster and mouse cell lines. Int J Oncol 4:49-54.
33. Olivero OA, Anderson LM, Diwan BA, Haines DC, Harbaugh SW, Moskal TJ, Jones AB, Rice JM, Riggs CW, Logsdon D, Yuspa SH, Poirier MC. 1997. Transplacental effects of 3′-azido-2′,3′-dideoxythymidine (AZT): Tumorgenicity in mice and genotoxicity in mice and monkeys. J Natl Cancer Inst 89:1602-1608.
34. Olivero OA, Shearer GM, Chougnet CA, Kovacs AAS, Landay AL, Baker R, Stek AM, Khoury MM, Proia LA, Kessler HA, Sha BE, Tarone RE, Poirier MC. 1999. Incorporation of zidovudine into leukocyte DNA from HIV-1-positive adults and pregnant women, and cord blood from infants exposed in utero. AIDS 13:919-925.
35. Olivero OA, Shearer GM, Chougnet CA, Kovacs AA, Baker R, Stek AM, Khoury MM, Poirier MC. 2000. Incorporation of zidovudine into cord blood DNA of infants and peripheral blood DNA of their HIV-1-positive mothers. Ann NY Acad Sci 918:262-268.
36. Olivero OA, Meng Q, Humsi JA, Walker VE, Poirier MC. 2002. Incorporation of the nucleoside analogue (NA) AZT and 3TC into cord blood-DNA from infants of HIV-1-infected mothers taking Combivir. In Proceedings of the 6th International Conference on Malignancies in AIDS and Other Immunodeficiencies: Basic, Epidemiologic and Clinical Research, Bethesda, MD, April 22-24, 2002.
37. O'Neill JP, Gundel RM, Trombley LM, Walker VE. 2001. HPRT mutant frequency and mutation spectra in newborns with perinatal exposure to antiviral drugs. Environ Mol Mutagen 37 (Suppl 32):58.
38. Peter K, Gambetoglio JG. 1998. Intracellular phosphorylation of zidovudine (ZDV) and other nucleoside reverse transcriptase inhibitors (RTI) used for human immunodeficiency virus (HIV) infection. Pharm Res 15:819-825.
39. Peter K, Lalezari P, Gambertoglio JG. 1996. Quantification of zidovudine and individual zidovudine phosphates in peripheral blood mononuclear cells by a combined isocratic high performance liquid chromatography radioimmunoassay method. J Pharm Biomed Anal 14:491-499.
40. Poirier MC, Patterson TA, Slikker W Jr, Olivero OA. 1999. Incorporation of 3′-azido-3′-deoxythymidien (AZT) into fetal DNA, fetal tissue distribution of drug after infusion of pregnant late-term rhesus macaques with a human-equivalent AZT dose. J Acquir Immune Defic Syndr 15:477-483.
41. Poirer MC, Olivero OA, Walker DM, Walker VE. 2004. Perinatal genotoxicity and carcinogenicity of anti-retroviral nucleoside analog drugs. Toxicol Appl Pharmacol 199:151-161.
42. Resetar A, Spector T. 1989. Glucuronidation of 3′-azido-3′- deoxythymidine: Human and rat enzyme specificity. Biochem Pharmacol 38:1389-1393.
43. Robbins BL, Rodman J, McDonald C, Srinivas RV, Flynn PM, Fridland A. 1994. Enzymatic assay for measurement of zidovudine triphosphate in peripheral blood mononuclear cells. Antimicrob Agents Chemother 38:115-121.
44. Robbins BL, Waibel BA, Fridland A. 1996. Quantitation of intracellular of zidovudine phosphates by use of combined cartridge-radioimmunoassay methodology. Antimicrob Agents Chemother 40:2651-2654.
45. Rodman JH, Robbins B, Flynn PM, Fridland A. 1996. A systemic and cellular model for zidovudine plasma concentrations and intracellular phosphorylation in patients. J Infect Dis 174:490-499.
46. Rodman JH, Flynn PM, Robbins B, Jimenez E, Bardeguez AD, Rodriguez JF, Blanchard S, Fridland A. 1999. Systemic pharmacokinetics and cellular pharmacology of Zidovudine in human immunodeficiency virus type 1-infected women and newborn infants. J Infect Dis 180:1844-1850.
47. Rodriguez Orengo JF, Santana J, Febo I, Diaz C, Rodriguez JL, Garcia R. Font E, Rosario O. 2000. Intracellular studies of the nucleoside reverse transcriptase inhibitor active metabolites: A review. P R Heath Sci J 19:19-27.
48. Sale M, Sheiner SM, Volberding P, Blasche TF. 1993. Zidovudine response relationships in early human immunodeficiency virus infection. Clin Pharmacol Ther 54:556-566.
49. Sharma M, Jain R, Inonescu E, Darnowski JW. 1995. Quantitative analysis of 3′-azido-3′-deoxythymidine incorporation into DNA in human colon tumor cells. Bioconjug Chem 6:536-540.
50. Sommadossi J, Carlisle R, Zhou Z. 1989. Cellular pharmacology of 3′-azido-3′-deoxythymidine with evidence of incorporation into DNA of human bone marrow cells. Mol Pharmacol 36:9-14.
51. Snyder S, D'Argenio DZ, Weislow O, Bilello JA, Drusano GL. 2000. The triple combination indinavir-zidovudine-lamivudine is highly synergistic. Antimicrob Agents Chemother 44:1051-1058.
52. Sperling RS, Shapiro DE, Coombs RW, Todd JA, Herman SA, McSherry GD, O'Sullivan MJ, Van Dyke RB, Jimenez E, Rouzioux C, Flynn PM, Sullivan JL, for the Pediatric AIDS Clinical Trials Group Protocol 076 Study Group. 1996. Maternal viral load, zidovudine treatment, and the risk of transmission of human immunodeficiency virus type 1 from mother to infant. N Engl J Med 335:1621-1629.
53. St Clair M, Richards C, Spector T, Weinhold K, Miller W, Langlois A, Furman P. 1987. 3′-Azido-3′-deoxythymidine triphosphate as an inhibitor and substrate of purified human immunodeficiency virus reverse transcriptase. Antimicrob Agents Chemother 31:1972-1977.
54. Stein DS, Moore KHP. 2001. Reviews of therapeutics. Phosphorylation of nucleoside analog antiretrovirals: A review for clinicians. Pharmacotherapy 21:10-34.
55. Stretcher BN, Pesce AJ, Hurtubise PE, Frame PT. 1992. Pharmacokinetics of zidovudine phosphorylation in patients infected with the human immunodeficiency virus. Ther Drug Monit 14:281-285.
56. Sussman HE, Olivero OA, Meng Q, Pietras SM, Poirier MC, O'Neill JP, Finette BA, Bauer MJ, Walker VE. 1999. Genotoxicity of 3′-azido-3′- deoxythymidine in the human lymphoblastoid cell line, TK6: Relationships between DNA incorporation, mutant frequency, and spectrum of deletion mutations in HPRT. Mutat Res 429:249-259.
57. Thevanayagam LN, Jayewardene AL, Gambertoglio JG. 2000. The stability of intracellular zidovudine and its anabolites in extracts of peripheral blood mononuclear cells (PBMCs). J Pharm Biomed Anal 22:597-603.
58. Tornevik Y, Jacobsson B, Britton S, Eriksson S. 1991. Intracellular metabolism of 3′azidothymidine in isolated human peripheral blood mononuclear cells. AIDS Res Hum Retroviruses 7:751-759.
59. Torres SM, Walker DM, Carter MM, Cook DL Jr, McCash CL, Cordova EM, Olivero OA, Poirer MC, Walker VE. 2007. Mutagenicity of zidovudine, lamivudine, and abacavir following in vitro exposure of CD-I mice to single agents or drug combinations. Environ Mol Mutagen 48:224-238.
60. Vazquez-Padua MA, Starnes MC, Cheng YC. 1990. Incorporation of 3′-azido-3′-deoxythymidine into cellular DNA, its removal in a human leukemic cell line. Cancer Commun 2:55-62.
61. VonTungeln LS, Williams LD, Doerge DR, Shaddock JG, McGarrity LJ, Morris SM, Mittelstaedt RA, Heflich RH, Beland FA. 2007. Transplacental drug transfer and frequency of Tk and Hprt lymphocyte mutants and peripheral blood micronuclei in mice treated transplacentally with zidovudine and lamivudine. Environ Mol Mutagen 48:258-269.
62. Walker DM, Malarkey DE, Seilkop SK, Ruecker FA, Funk KA, Wolfe MJ, Treanor CP, Foley JF, Hahn FF, Hardisty JF, Walker VE. 2007. Transplacental carcinogenicity of 3′-Azido-3′-deoxythymidine in B6C3F1 mice and F344 rats. Environ Mol Mutagen 48:283-298.
63. Walker VE, Wade N, Abrams E, Ness RB. 2001. Observational cohort study of the genotoxic risks arising from perinatal NRTI therapies. Environ Mol Mutagen 37 (Suppl 32):77.
64. Watts DH. 2006. Treating HIV during pregnancy. An update on safety issues. Drug Saf 29:467-490.