The effects of three 1-(halogenalkoxy)alkyl-5-fluorouracil derivatives on cultured mouse lymphoma cells were studied and compared with those of N-methyl-bis-(2-chloroethyl)amine hydrochloride (Lost). The derivatives exert only little influence on cell proliferation and cell volume. However, all derivatives cause a concentration-dependent nucleus contraction, probably due to DNA cross-linkings. Bromodesoxyuridine modulates the effects of the derivatives on the DNA, leading to swelling of the nucleus, which may be caused by DNA strand-breaks. It is suggested that the derivatives exert synergistic effects with other factors. It is concluded that these studies are suitable for the prescreening of agents to be investigated in mutagenicity tests.
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