Tamoxifen does not form detectable DNA adducts in white blood cells of breast cancer patients

Carcinogenesis

Volumn 17, Issue 5, 1996, Pages 1149-1152

  Phillips, David H ^a   Hewer, Alan ^a   Grover, Philip L ^a   Poon, Grace K ^a,b   Carmichael, Paul L ^a  

^a INSTITUTE OF CANCER RESEARCH   (United Kingdom)

^b GLAXOSMITHKLINE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

DNA; PHOSPHORUS 32; TAMOXIFEN;

ARTICLE; BREAST CANCER; CANCER ADJUVANT THERAPY; CLINICAL ARTICLE; CONTROLLED STUDY; DNA ADDUCT; DRUG DNA INTERACTION; FEMALE; HUMAN; HUMAN CELL; ISOTOPE LABELING; LEUKOCYTE; PRIORITY JOURNAL;

ADULT; AGED; AGED, 80 AND OVER; ANTINEOPLASTIC AGENTS, HORMONAL; BREAST NEOPLASMS; DNA ADDUCTS; ESTROGEN ANTAGONISTS; FEMALE; HUMANS; LEUKOCYTES; MIDDLE AGED; TAMOXIFEN;

EID: 0029903222     PISSN: 01433334     EISSN: None     Source Type: Journal    
DOI: 10.1093/carcin/17.5.1149     Document Type: Article

References (26)

1. Hard,G.C., Iatropoulos,M.J., Jordan,K., Radi,L., Kaltenberg,O.P., Imondi,A.R. and Williams,G.M. (1993) Major difference in the hepato carcinogenicity and DNA adduct forming ability between toremifene and tamoxifen in female Crl:CD(BR) rats. Cancer Res., 53, 4534-4541.
2. Hirsimäki,P., Hirsimäki,Y., Nieminen,L. and Payne,B.J. (1993) Tamoxifen induces hepatocellular carcinoma in rat liver: a 1-year study with two antiestrogens. Arch. Toxicol., 67, 49-54.
3. Greaves,R. Goonetilleke,R., Nunn,G., Topham,J. and Orton,T. (1993) Twoyear carcinogenicity study of tamoxifen in Alderley Park Wistar-derived rats. Cancer Res., 53, 3919-3924.
4. Fomander,T. et al. (1989) Adjuvant tamoxifen in early breast cancer: occurrence of new primary cancers. Lancet, i. 117-120.
5. Andersson,M., Storm,H.H. and Mouridsen,H.T. (1992) Carcinogenic effects of adjuvant tamoxifen treatment for early breast cancer. Acta Oncol., 31, 259-263.
6. Fisher,B., Costantino,J.P., Redmond,C.K., Fisher,E.R., Wickerham,D.L., Cronin,W.M. and other NSABP contributors (1994) Endometrial cancer in tamoxifen-treated breast cancer patients: findings from the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-14. J. Natl Cancer Inst., 86, 527-537.
7. Rutqvist,L.E., Johansson,H., Signomklao,T., Johansson,U., Fomander,T. and Wilking,N. (1995) Adjuvant tamoxifen therapy for early stage breast cancer and second primary malignancies. J. Natl Cancer Inst., 87, 645-651.
8. Jordan,V.C. (1995) Tamoxifen: toxicities and drug resistance during the treatment and prevention of breast cancer. Annu. Rev. Pharmacol. Toxicol., 35, 195-211.
9. Porter,G.A., McCague,R. and Jarman,M. (1994) A mechanistic hypothesis for DNA adduct formation by tamoxifen following hepatic oxidative metabolism. Carcinogenesis, 15, 439-442.
10. 5-ethyl]-tamoxifen implicates α-hydroxylation of the ethyl group as a major pathway of tamoxifen activation to a liver carcinogen. Carcinogenesis, 15, 1487-1492.
11. Phillips,D.H., Carmichael,P.L., Hewer,A., Cole,K.J. and Poon,G.K. (1994) α-Hydroxytamoxifen, a metabolite of tamoxifen with exceptionally high DNA-binding activity in rat hepatocytes. Cancer Res., 54, 5518-5522.
12. Osborne,M.R., Hewer,A., Hardcastle,I.R., Carmichael,P.L. and Phillips,D.H. (1996) Identification of the major tamoxifen-deoxyguanosine adduct formed in the liver DNA of rats treated with tamoxifen. Cancer Res., 57, 66-71.
13. Phillips,D.H., Carmichael,P.L., Hewer,A., Cole,K.J., Hardcastle,I.R., Poon,G.K., Keogh,A. and Strain,A.J. (1996) Activation of tamoxifen and its metabolite α-hydroxytamoxifen to DNA-binding products: comparisons between human, rat and mouse hepatocytes. Carcinogenesis, 17, 89-94.
14. Sargent,L.M., Dragan,Y.P., Bahnub,N., Wiley,J.E., Sattler,C.A., Schroeder,P., Sattler,G.L., Jordan,V.C. and Pitot,H.C. (1994) Tamoxifen induces hepatic aneuploidy and mitotic spindle disruption after a single in vivo administration to female Sprague-Dawley rats. Cancer Res., 54, 3357-3360.
15. Crofton-Sleigh,C., Doherty,A., Ellard,S., Parry,E.M. and Venitt,S. (1993) Micronucleus assays using cytochalasin-blocked MCL-5 cells, a proprietary human cell line expressing five human cytochromes P-450 and microsomal epoxide hydrolase. Mutagenesis, 8, 363-372.
16. Styles,J.A., Davies,A., Lim,C.K., de Matteis,F., Stanley,L.A., White,I.N.H., Yuan,Z.-X. and Smith,L.L. (1994) Genotoxicity of tamoxifen, tamoxifen epoxide and toremifene in human lymphoblastoid cells containing human cytochrome P450s. Carcinogenesis, 15, 5-9.
17. Langan-Fahey,S.M., Tormey,D.C. and Jordan,V.C. (1990) Tamoxifen metabolites in patients on long-term adjuvant therapy for breast cancer. Eur. J. Cancer, 26, 883-888.
18. Poon,G.K., Chui,Y.C., McCague,R., Lønning,P.E., Feng,M.G., Rowlands,M.G. and Jarman,M. (1993) Analysis of Phase I and Phase II metabolites of tamoxifen in breast cancer patients. Drug Metab. Dispos., 21, 1119-1124.
19. Hemminki,K., Widlak,P. and Hou,S.-M. (1995) DNA adducts caused by tamoxifen and toremifene in human microsomal system and lymphocytes in vitro. Carcinogenesis, 16, 1661-1664.
20. Gupta,R.C. (1984) Non-random binding of the carcinogen N-hydroxy-2-acetylaminofluorene to repetitive sequences of rat liver DNA in vivo. Proc. Natl Acad. Sci. USA. 81, 6943-6947.
21. Phillips,D.H., Hewer,A. and Grover,P.L. (1986) Aromatic DNA adducts in human bone marrow and blood leukocytes. Carcinogenesis, 7, 2071-2075.
22. Jordan,V.C., Bain,R.R., Brown,R.R., Gosden,B. and Santos,M.A. (1983) Determination and pharmacology of a new hydroxylated metabolite of tamoxifen observed in patient sera during therapy for advanced breast cancer. Cancer Res., 43, 1446-1450.
23. Trump,D.L., Smith,D.C., Ellis,P.G., Rogers,M.R., Schold,S.C., Winer,E.P., Panell,T.J., Jordan,V.C. and Fine,R.L. (1992) High oral dose tamoxifen, a potential multidrug-resistance-reversal agent: phase I trial in combination with vinblastine. J. Natl Cancer Inst., 84, 1811-1816.
24. White,I.N.H., de Matteis,F., Davies,A., Smith,L.L., Crofton-Sleigh,C., Venitt,S., Hewer,A. and Phillips,D.H. (1992) Genotoxic potential of tamoxifen and analogues in female Fischer F344/n rats, DBA/2 and C57B1/6 mice and in human MCL-5 cells. Carcinogenesis, 13, 2197-2203.
25. 32P-Postlabelled DNA adducts in liver obtained from women treated with tamoxifen. Carcinogenesis, 16, 1651-1654.
26. Carmichael,P.L., Ugwumadu,A.H.N., Neven,P., Hewer,A., Poon,G.K. and Phillips,D.H. (1996) Lack of genotoxicity of tamoxifen in human endometrium. Cancer Res., 56, in press.