Induction of sister chromatid exchanges in human lymphocytes by DTPA.

The chelating agent, diethylenetriaminepentaacetic acid (DTPA) is a non-registered drug used in the treatment of over-exposure to heavy metals such as iron, zinc and lead (Fahey et al., 1961; Brugsch et al., 1965). DTPA has also been used on a few occasions in the United Kingdom when individuals have inhaled plutonium dust or received contaminated wounds (Schofield and Dolphin, 1974). These patients received a series of intravenous injections of 0-25 g of calcium-DTPA in 20 ml of physiological saline. At concentrations of 6-30 times the therapeutic dose DTPA produces transient toxic effects in the liver and kidneys of mice (Morgan and Smith, 1974). It may cause the release of proteins from cell membranes (Stack and Fox, 1972) and there is some evidence to suggest that chelating agents may induce chromosome aberrations in Vicia faba (Cohn, 1961; Michaelis et al., 1962). It is possible, therefore, that DTPA may be hazardous to humans; this study investigates the risk involved in the use of this drug. Sister chromatid exchange (SCE) induction is one of many short-term screening tests which are likely to be used in the initial testing of new drugs for possible mutagenic side effects (Bridges, 1976). Although the procedure is reliable, quick and relatively simple it does possess several shortcomings. In common with other in vitro mutagenicity tests it is not sensitive to certain known mutagens, such as chloramphenicol, whose metabolites are the agents causing damage. False negative results may be avoided in some instances by including metabolically active liver microsomes in the cell culture (Stetka and Wolff, 1976). The high background incidence of SCEs, presumably caused by the necessary addition of a base analogue, and the possibility of synergism between the test drug and