Response of a High-glucuronidase Human Tumour Xenograft to Aniline Mustard

Overview

Journal Br J Cancer

Specialty Oncology

Date 1982 Jan 1

PMID 7059462

Citations 1

Authors

H M Warenius

P Workman

N M Bleehen

Affiliations

Soon will be listed here.

Abstract

The HT29R colonic adenocarcinoma xenograft has been shown to be rich in the enzyme beta-glucuronidase. Experiments in rodent systems have demonstrated a marked anti-tumour effect of the drug aniline mustard (AM) on tumours with high levels of this enzyme (e.g. the plasmacytomas PC5 and PC6). We have found that AM is no more effective than its analogue paramethyl aniline mustard (PMAM) or other alkylating agents against the HT29R xenograft. Amongst the possible explanations for this may be: (1) The wide shoulder on the cell-survival curve shown for exposure to alkylating agents of HT29R in vivo. (2) Lack of correlation between physiological availability of beta-glucuronidase and the high levels measured by the standard assay. (3) Increased beta-glucuronidase levels in host mouse marrow, making the latter potentially more susceptible to AM damage.

Citing Articles

The in vitro metabolism of irinotecan (CPT-11) by carboxylesterase and beta-glucuronidase in human colorectal tumours.

Tobin P, Clarke S, Seale J, Lee S, Solomon M, Aulds S Br J Clin Pharmacol. 2006; 62(1):122-9.

PMID: 16842384 PMC: 1885078. DOI: 10.1111/j.1365-2125.2005.02477.x.

References

WHISSON M, Connors T . Cure of mice bearing advanced plasma cell tumours with aniline mustard. Nature. 1965; 206(985):689-91. DOI: 10.1038/206689a0. View

Connors T, WHISSON M . Cure of mice bearing advanced plasma cell tumours with aniline mustard: the relationship between glucuronidase activity and tumour sensitivity. Nature. 1966; 210(5038):866-7. DOI: 10.1038/210866b0. View

Healy J . The disease, myelomatosis. Ir J Med Sci. 1968; 7(5):211-26. DOI: 10.1007/BF02958759. View

Kyle R, Costa G, Cooper M, Ogawa M, Silver R, GLIDEWELL O . Evaluation of aniline mustard in patients with multiple myeloma. Cancer Res. 1973; 33(5):956-60. View

Connors T, Farmer P, Foster A, Gilsenan A, Jarman M, Tisdale M . Metabolism of aniline mustard (N,N-di-(2-chloroethyl)aniline). Biochem Pharmacol. 1973; 22(16):1971-80. DOI: 10.1016/0006-2952(73)90079-8. View

Kopper L, STEEL G . The therapeutic response of three human tumor lines maintained in immune-suppressed mice. Cancer Res. 1975; 35(10):2704-13. View

von Kleist S, CHANY E, Burtin P, King M, Fogh J . Immunohistology of the antigenic pattern of a continuous cell line from a human colon tumor. J Natl Cancer Inst. 1975; 55(3):555-60. DOI: 10.1093/jnci/55.3.555. View

Workman P, Ball C, Double J . Enzyme activated anti-tumour agents- II. The role of alkaline phosphatase in the release of p-hydroxyaniline mustard from its phosphate conjugate in cells in culture. Biochem Pharmacol. 1976; 25(10):1139-44. DOI: 10.1016/0006-2952(76)90360-9. View

Young C, Yagoda A, Bittar E, Smith S, GRABSTALD H, Whitmore W . Therapeutic trial of aniline mustard in patients with advanced cancer. Comparison of therapeutic response with cytochemical assessment of tumor cell beta-glucuronidase activity. Cancer. 1976; 38(5):1887-95. DOI: 10.1002/1097-0142(197611)38:5<1887::aid-cncr2820380504>3.0.co;2-#. View

10.

Double J, Workman P . A new high-glucuronidase mouse tumor curable by aniline mustard therapy. Cancer Treat Rep. 1977; 61(5):909-11. View

11.

Workman P, Double J . Drug latentiation in cancer chemotherapy. Biomedicine. 1978; 28(5):255-62. View

12.

Carl P, CHAKRAVARTY P, Katzenellenbogen J, Weber M . Protease-activated "prodrugs" for cancer chemotherapy. Proc Natl Acad Sci U S A. 1980; 77(4):2224-8. PMC: 348685. DOI: 10.1073/pnas.77.4.2224. View

13.

Warenius H, Freedman L, Bleehen N . The response of a human tumour xenograft to chemotherapy: intrinsic variation between tumours and its significance in planning experiments. Br J Cancer Suppl. 1980; 4:128-32. PMC: 2149238. View

14.

WHISSON M, Connors T . DRUG-INDUCED REGRESSION OF LARGE PLASMA CELL TUMOURS. Nature. 1965; 205:406. DOI: 10.1038/205406a0. View

15.

Harper N . Drug latentiation. J Med Pharm Chem. 1959; 1:467-500. DOI: 10.1021/jm50006a005. View