Time-course study of the immunotoxic effects of the anticancer drug chlorambucil in the rat.

Pearse, G., Pietersma, A., Cunliffe, H., Foster, J.R., Turton, J.A., Derbyshire, N. and Randall, K.J. (2009) Time-course study of the immunotoxic effects of the anticancer drug chlorambucil in the rat. Toxicologic Pathology, 37 (7). pp. 887-901. 10.1177/0192623309347907.

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DOI: 10.1177/0192623309347907


In 2005, the International conference on harmonization (ICH) recommended that all new human pharmaceuticals be tested for unintended immunomodulatory potential via a tiered approach. Included in this approach is a semiquantitative description of changes in the separate compartments of lymphoid tissue (also called enhanced histopathology). Chlorambucil was administered to Hanover Wistar rats at regular time points, followed by a treatment-free (recovery) period. Groups of treated and control animals were sacrificed regularly during both the treatment and recovery periods. Selected tissues were removed, weighed fresh and fixed in formalin, processed, and stained with hematoxylin and eosin. Blood samples and bone marrow smears were also obtained. With the use of enhanced histopathology, a description of the changes in lymphoid tissues and bone marrow was used as a means of assessing the susceptibility, and recovery, of the different lymphoid cell populations over time. A correlation with organ weights, flow cytometry data, and bone marrow cytology was achieved. The administration of chlorambucil in the Hanover Wistar rat provided a useful tool to examine the rate and sequence of changes in the lymphoid organs and bone marrow during treatment with, and the recovery from the effects of, a potent immunosuppressive agent.

Item Type:Article
Uncontrolled Keywords:chlorambucil immunosuppression immunotoxicity lymphoid organs bone marrow rat
Departments, units and centres:Department of Pharmacology > Centre for Toxicology
ID Code:1409
Journal or Publication Title:Toxicologic Pathology
Deposited By:Library Staff
Deposited On:10 Feb 2010 12:20
Last Modified:24 Feb 2012 11:18

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