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Updated: Aug 4, 2026

Measurement of Heme Synthesis Levels in Mammalian Cells
Published on: July 9, 2015
Hydroxyethylation of hemoglobin by 1-(2-chloroethyl)-1-nitrosoureas
E Bailey1, P B Farmer, Y S Tang
1MRC Toxicology Unit, Carshalton, Surrey, U.K.
Abstract:
Following treatment of cancer patients with three 1-(2-chloroethyl)-1-nitrosoureas, hemoglobin was isolated and analyzed by GC-MS for N-(2-hydroxyethyl)-N-terminal valine. This alkylated amino acid was liberated as a (pentafluorophenyl)thiohydantoin from the hemoglobin by a modified Edman degradation procedure. Following intravenous infusion of fotemustine [diethyl[1-[3-(2-chloroethyl)-3-nitrosoureido]ethylphosphonate] (ca. 90 mg/m2) the levels of (hydroxyethyl)valine in two patients increased steadily, reaching a peak of ca. 300 pmol/g after 6 h. In a further five patients receiving fotemustine (100 mg/m2) alkylation levels 24 h after treatment ranged from 132 to 1524 pmol/g of globin. Treatment with TCNU [1-(2-chloroethyl)-3-[2-[(dimethylamino)sulfonyl]ethyl]-1- nitrosourea] or ACNU [1-[(4-amino-2-methylpyrimidin-5-yl)methyl]-3-(2-chloroethyl)-3- nitrosourea] resulted in similar increases in (hydroxyethyl)valine in hemoglobin, although the amounts (as with fotemustine) showed considerable interindividual variation. It appears that the measurement of (hydroxyethyl)valine in hemoglobin may be a suitable monitor of exposure to hydroxyethylating agents during (chloroethyl)nitrosourea chemotherapy.
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