The genotoxic potential of glutaraldehyde in mammalian cells in vitro in comparison with formaldehyde.
Glutaraldehyde (GA) induces DNA-protein crosslinks (DPX), but conflicting results have been reported with regard to other genotoxic and mutagenic effects in mammalian cells in vitro. We, therefore, characterized the genotoxic and mutagenic potential of GA in V79 cells. Using the alkaline comet assay we demonstrated the induction of DPX by GA (reduction of gamma ray-induced DNA migration) at a concentration of 10 microM and above. The standard comet assay did not reveal a significant DNA strand-breaking activity of GA. Cross-linking concentrations of GA were also cytotoxic, i.e. inhibited cell growth of treated V79 cultures. Interestingly, a small but statistically significant increase in sister chromatid exchange (SCE) and micronuclei (MN) was already measured at lower concentrations (2 and 5 microM). FISH analysis revealed that the majority of GA-induced MN was due to chromosome breaks. We also compared the genotoxic activity of GA to that of formaldehyde (FA). Similar to GA, FA-induced DPX, SCE and MN, but distinct differences exist with regard to the sensitivity of the endpoints and the relationship between genotoxicity and cytotoxicity. However, the differences in genotoxicity cannot readily explain the different carcinogenic activities of the two compounds.
Speit
Günter
G
Universität Ulm, Institut für Humangenetik, Ulm, Germany. guenter.speit@uni-ulm.de
Neuss
Simone
S
Schütz
Petra
P
Fröhler-Keller
Manuela
M
Schmid
Oliver
O
D000818:Animals; D002460:Cell Line; D020552:Comet Assay; D053960:DNA Breaks / Q000187:drug effects; D004249:DNA Damage; D005557:Formaldehyde / Q000633:toxicity*; D005976:Glutaral / Q000633:toxicity*; D017404:In Situ Hybridization, Fluorescence; D015162:Micronucleus Tests; D012854:Sister Chromatid Exchange / Q000187:drug effects*
D005557:Formaldehyde; D005976:Glutaral