{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T17:15:20Z","timestamp":1767374120483},"reference-count":80,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2006,1,23]],"date-time":"2006-01-23T00:00:00Z","timestamp":1137974400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J Experimental Path"],"published-print":{"date-parts":[[2006,2]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Aplastic anaemia (AA) in man is an often fatal disease characterized by pancytopenia of the peripheral blood and aplasia of the bone marrow. AA is a toxic effect of many drugs and chemicals (e.g. chloramphenicol, azathioprine, phenylbutazone, gold salts, penicillamine and benzene). However, there are no widely used or convenient animal models of drug\u2010induced AA. Recently, we reported a new model of chronic bone marrow aplasia (CBMA\u2003=\u2003AA) in the busulphan (BU)\u2010treated mouse: eight doses of BU (10.50\u2003mg\/kg) were administered to female BALB\/c mice over a period of 23 days; CBMA was evident at day 91\/112 post\u2010dosing with significantly reduced erythrocytes, platelets, leucocytes and nucleated bone marrow cell counts. However, mortality was high (49.3%). We have now carried out a study to modify the BU\u2010dosing regime to induce CBMA without high mortality, and investigated the patterns of cellular responses in the blood and marrow in the post\u2010dosing period. Mice (<jats:italic>n<\/jats:italic>\u2003=\u200364\/65) were dosed 10 times with BU at 0 (vehicle control), 8.25, 9.0 and 9.75\u2003mg\/kg over 21 days and autopsied at day 1, 23, 42, 71, 84, 106 and 127 post\u2010dosing (<jats:italic>n<\/jats:italic>\u2003=\u20037\u201315); blood and marrow samples were examined. BU induced a predictable bone marrow depression at day 1 post\u2010dosing; at day 23\/42 post\u2010dosing, parameters were returning towards normal during a period of recovery. At day 71, 84, 106 and 127 post\u2010dosing, a stabilized, late\u2010stage, nondose\u2010related CBMA was evident in BU\u2010treated mice, with decreased erythrocytes, platelets and marrow cell counts, and increased MCV. At day 127 post\u2010dosing, five BU\u2010treated mice showed evidence of lymphoma. In this study, mortality was low, ranging from 3.1% (8.25\u2003mg\/kg BU) to 12.3% (9.75\u2003mg\/kg BU). It is concluded that BU at 9.0\u2003mg\/kg (or 9.25\u2003mg\/kg) is an appropriate dose level to administer (10 times over 21 days) to induce CBMA at approximately day 50\u2013120 post\u2010dosing.<\/jats:p>","DOI":"10.1111\/j.0959-9673.2006.00455.x","type":"journal-article","created":{"date-parts":[[2006,1,23]],"date-time":"2006-01-23T16:15:15Z","timestamp":1138032915000},"page":"49-63","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Further development of a model of chronic bone marrow aplasia in the busulphan\u2010treated mouse"],"prefix":"10.1111","volume":"87","author":[{"given":"John A.","family":"Turton","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William R.","family":"Sones","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles M.","family":"Andrews","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew M.","family":"Pilling","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas C.","family":"Williams","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gemma","family":"Molyneux","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sian","family":"Rizzo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward C.","family":"Gordon\u2010Smith","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frances M.","family":"Gibson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,1,23]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0308-2261(21)00042-4"},{"key":"e_1_2_6_3_1","first-page":"111","volume-title":"Haematology of Infancy and Childhood","author":"Alter B.P.","year":"1998"},{"key":"e_1_2_6_4_1","unstructured":"AndrewsC.M.(2000)Studies on the haemotoxicity of busulphan and chloramphenicol in the B6C3F1 mouse.PhD Thesis.University of London."},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00368113"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02658695"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02642503"},{"key":"e_1_2_6_8_1","volume-title":"Theory and Practice of Histological Techniques","author":"Bancroft J.D.","year":"1990"},{"key":"e_1_2_6_9_1","first-page":"26","volume-title":"Aplastic Anaemia","author":"Benestad H.","year":"1979"},{"key":"e_1_2_6_10_1","first-page":"646","article-title":"Busulphan and chloramphenicol induced T cell lymphoma: cell surface characteristics and functional properties","volume":"64","author":"Bhoopalam N.","year":"1986","journal-title":"Clin. 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