Distribution of bratton-marshall-positive material in mice following intravenous injections of nitrosoureas

Abstract

As determined by a colorimetric assay measuring parent compounds plus ether-extractable nitroso-containing metabolites, N,N'-bis(2-chloroethyl)-N-nitrosourea (BCNU) disappeared more rapidly than N-(2-chloroethyl)-N'cyclohexyl-N-nitrosourea (CCNU) and N-(2-chloroethyl)-N'-(4-transmethylcyclohexyl)-N-nitrosourea (MeCCNU) and their products from the tissues of mice injected IV. Assay of selected samples by high-pressure liquid chromatography revealed that the colorimetric assay for BCNU was specific in that the two assays gave equivalent results. Following IV-injections of CCNU and MeCCNU, however, levels of the parent compounds decreased much more rapidly than the total, color-producing material. Of seven tissues, the largest Cxt values for BCNU, as determined by the colorimetric assay, were noted for blood (442 microgram-min/ml) and large intestine (285 microgram-min/g). Liver (29 microgram-min/g) had the lowest Cxt value, reflecting rapid metabolism of the compound by this organ. Color-producing material related to CCNU disappeared from the solid tissues of mice in a manner generally parallel to that for blood. Of the Cxt values for this compound and its products, those for lung (1753 microgram-equivalents-min/g), kidney (1633 microgram-equivalents-min/g), and small intestine (1557 microgram-equivalents-min/g) were highest. Consistent with its slower rate of metabolism, MeCCNU and its color-producing metabolites remained in most tissues of mice for 12 h following injection. Except for brain (1434 microgram-equivalents-min/g), Cxt values for this nitrosourea and its metabolites in tissues were higher than those of blood (5485 microgram-equivalents-min/ml), with kidney (15,324 micrograms-equivalents-min/g), liver (12,921 microgram-equivalents-min/g), and large intestine (11,501 microgram-equivalents-min/g) being highest. For each nitrosourea, a fair correlation was observed between the Cxt values for tissues and the toxic and/or antitumor effects at those sites.

Magnetic Oleosome as a Functional Lipophilic Drug Carrier for Cancer Therapy

“…Not only does carmustine have a high lipid solubility, but it also has been shown to readily cross the blood–brain barrier, leading it to become one of the most clinically used drugs for brain tumor treatment . However, it is not popularly used for other malignant tumors due to its lack of target specificity and easy cell membrane fusion in normal tissues during regular body circulation . By varying the volume ratio of oleosome, we found that 1:50 (oleosome/PBS) or less ratio of oleosome solution had a negligible effect on survivability under the daily intravenous injection condition, whereas over 1:10 ratio of oleosome solution was found to be toxic after 1 h injection by the obstruction of blood flow.…”

Resorbable polymer microchips releasing BCNU inhibit tumor growth in the rat 9L flank model

“…High-pressure liquid chromatography (HPLC) and a colorimetric assay using the Bratton-Marshall reagent can both be used to quantify BCNU (2,(26)(27)(28) . The Bratton-Marshall method was preferred for this study to quantify the intact BCNU molecule due to ability to process larger numbers of samples in parallel.…”

BCNU stability as a function of ethanol concentration and temperature

“…A simple and inexpensive colorimetric BCNU assay [8][9], based upon the sulfanilamide assay developed by Bratton and Marshall [10] was utilized. A major advantage of this assay derivatization was that only the intact BCNU molecule was quantitated.…”