Evaluation of the genotoxic potential of glutaraldehyde.
The cytotoxic and genotoxic effects of glutaraldehyde were studied in vitro in the human TK6 lymphoblast cell line and in primary cultures of rat hepatocytes. TK6 lymphoblasts were exposed to glutaraldehyde for 2 hr in serum-free GSH-free media. Cytotoxic effects were observed at concentrations as low as 10 microM with only 10% cell survival at 20 microM. Alkaline elution studies indicated that glutaraldehyde-induced DNA-protein crosslinking increased linearly over the concentration range from 0 to 25 microM. Glutaraldehyde-induced mutations were assessed at the thymidine kinase locus over the same concentration range and reached a plateau at 10 microM of about six times the background mutant frequency. At equivalent levels of DNA-protein crosslinks and cytolethality, glutaraldehyde was mutagenic at approximately a one-seventh lower concentration than the rodent nasal carcinogen formaldehyde (Craft et al.; Mutation Research 176:147-155, 1987). Glutaraldehyde induced a marginal increase in unscheduled DNA synthesis in the in vitro hepatocyte DNA repair assay, but only at the two highest concentrations of 50 and 100 microM, indicating the induction of some DNA excision-repair activity. These data demonstrate that glutaraldehyde exhibits DNA-reactive genotoxic activity that may involve, at least in part, DNA-protein crosslinking in these cell culture models. These findings suggest the need to examine the potential carcinogenic activity of glutaraldehyde in appropriate inhalation studies.
St Clair
M B
MB
Chemical Industry Institute of Toxicology, Department of Experimental Pathology, Research Triangle Park, North Carolina 27709.
Bermudez
E
E
Gross
E A
EA
Butterworth
B E
BE
Recio
L
L
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003432:Cross-Linking Reagents / Q000737:chemistry; D004249:DNA Damage; D004260:DNA Repair; D005976:Glutaral / Q000737:chemistry / Q000633:toxicity*; D006801:Humans; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology; D008214:Lymphocytes; D008297:Male; D009153:Mutagens; D051381:Rats; D011916:Rats, Inbred F344
D003432:Cross-Linking Reagents; D009153:Mutagens; D005976:Glutaral