This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Morelli, D. Articles by Balsari, A. Search for Related Content PubMed PubMed Citation Articles by Morelli, D. Articles by Balsari, A.

Oral Administration of Anti-Doxorubicin Monoclonal Antibody Prevents Chemotherapy-induced Gastrointestinal Toxicity in Mice¹

Division of Experimental Oncology E [D. M., S. M., M. I. C.], Istituto Nazionale Tumori, and Institute of Pathology [A. B.], University of Milan, via Venezian 1, 20133 Milan, Italy

Gastrointestinal mucositis is a common and painful condition that afficts a proportion of cancer patients receiving chemotherapeutic drugs including anthracyclines, and it has become the dose-limiting toxicity for a number of chemotherapeutic regimens. The murine monoclonal antibody MAD11 recognizes the anthracycline doxorubicin, and systemic administration of this antibody in mice treated with doxorubicin was found previously to prevent the toxic effects of the drug. The purpose of this study was to determine whether gastrointestinal toxicity associated with doxorubicin can be reduced by oral administration of anti-doxorubicin MAD11 in mice. Our experiments show that orally administered MAD11 antibodies: (a) are essentially not absorbed in the blood circulation since less than 0.5% of protein-associated radioactivity was recovered from blood samples; (b) reduce the extent of doxorubicin-induced apoptosis in murine intestinal crypts, as determined by labeling strand breaks with modified nucleotides in an enzymatic reaction; and (c) reduce the body weight loss in mice treated with 12 mg/kg body weight of doxorubicin and decrease the early mortality in mice treated with 16 mg/kg body weight. This type of treatment may be useful in preventing anthracycline-induced gastrointestinal mucostis in cancer patients.

¹ Supported by the Associazione Italiana per la Ricerca sul Cancro and by Consiglio Nazionale Ricerche-progetto finalizzato Applicazioni Cliniche della Ricerca Oncologica.

² To whom requests for reprints should be addressed. Phone: +39-2-2390573; Fax: +39-2-2362692.

Received 12/ 1/95. Accepted 3/ 4/96.

This article has been cited by other articles:

				M. D. Gulkac, G. Akpinar, H. Ustun, and A. Ozon Kanli Effects of vitamin A on doxorubicin-induced chromosomal aberrations in bone marrow cells of rats Mutagenesis, May 1, 2004; 19(3): 231 - 236. [Abstract] [Full Text] [PDF]

				A. N. M. Wymenga, W. T. A. van der Graaf, L. S. Hofstra, F. K. L. Spijkervet, W. Timens, H. Timmer-Bosscha, W. J. Sluiter, A. H. J. A. W. van Buuren, N. H. Mulder, and E. G. E. de Vries Phase I Study of Transforming Growth Factor-{beta}3 Mouthwashes for Prevention of Chemotherapy-induced Mucositis Clin. Cancer Res., June 1, 1999; 5(6): 1363 - 1368. [Abstract] [Full Text] [PDF]