Combinations of chlorocatechols and heavy metals cause DNA degradation in vitro but must not result in increased mutation rates in vivo

Chlorocatechols introduced into the environment directly or as a result of degradation processes are highly toxic, particularly when combined with hea vy metals. With in vitro DNA degradation assays, the high reactivity of chl orocatechols combined with heavy metals could be shown, whereby copper was shown to be more active than iron. Structure-activity analysis showed that the degradation potential of the chlorocatechols decreased with an increasi ng number of chloratoms. The addition of reactive oxygen species scavengers allowed the identification of hydrogen peroxide as an important agent lead ing to DNA damage in this reaction. The potential of other reactive compoun ds, however, can neither be determined nor excluded with this approach. Exp osure of Escherichia coli and Salmonella typhimurium cultures to the same m ixtures of chlorocatechols and copper surprisingly did not lead to an enhan ced mutation rate. This phenomenon was explained by doing marker gene expre ssion measurements and toxicity tests with E. coli mutants deficient in oxi dative stress defense or DNA repair. In catechol-copper-exposed cultures an increased peroxide level could indeed be demonstrated, but the highly effi cient defense and repair systems of E. coli avoid the phenotypical establis hment of mutations. Increased mutation rates under chronic exposure, howeve r, cannot be excluded. (C) 1999 Wiley-Liss, Inc.