Synergistic DNA damaging effects of 4-nitroquinoline-1-oxide and non-effective concentrations of methyl methanesulfonate in human fibroblasts.
DNA damage and DNA repair in human fibroblasts induced by the combination mixture of the genotoxic agents methyl methanesulfonate (MMS) and 4-nitroquinoline-1-oxide (4-NQO) were studied using the comet assay and the unscheduled DNA synthesis (UDS), respectively. Cells were simultaneously treated for 1h with the no observed effect concentration (noec) of MMS and increasing concentrations of 4-NQO or vice versa. Different results were obtained with the two types of mixtures. When the noec of 4-NQO was combined with increasing concentrations of MMS, no combination effects were observed. However, in experiments with increasing concentrations of 4-NQO and the noec of MMS, an increase in DNA damage and repair (and an enhancement of cytotoxicity) was demonstrated. Quantitative analysis of the effects by the isobologram method confirmed synergistic responses in both tests. We are proposing interactive actions between 4-NQO and MMS, whereby 4-NQO facilitates the attack of MMS on the DNA bases.
Hömme
M
M
Carl von Ossietzky Universität Oldenburg, ICBM and FB 7, Postfach 2503, D-26111, Oldenburg, Germany.
Jacobi
H
H
Juhl-Strauss
U
U
Witte
I
I
D015112:4-Nitroquinoline-1-oxide / Q000633:toxicity*; D002460:Cell Line; D020552:Comet Assay; D004249:DNA Damage; D004260:DNA Repair; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008741:Methyl Methanesulfonate / Q000633:toxicity*; D009153:Mutagens / Q000633:toxicity*
D009153:Mutagens; D015112:4-Nitroquinoline-1-oxide; D008741:Methyl Methanesulfonate