Evaluation of the genotoxic potential of glutaraldehyde

Abstract

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.

Thermogelling bioadhesive scaffolds for intervertebral disk tissue engineering: Preliminary in vitro comparison of aldehyde-based versus alginate microparticle-mediated adhesion

“…The DNA amount isolated from 5 day cultures of HEK-293 cells seeded at 10 6 /ml with the various controls and growth medium is presented in Figure 5. With the incorporation of CS aldehyde, there was a significant decrease (p<0.05) in DNA content compared to PNIPAAm-g-CS, which is expected since aldehydes are known to induce cytotoxic response in cells [44] [45]. The addition of free gelatin (0.62 mg/mL polymer solution) to PNIPAAm-g-CS + CS aldehyde did not produce a significant change (p>0.05) in DNA content compared to PNIPAAm-g-CS + CS aldehyde, indicating that the use of gelatin to “end cap” the aldehyde groups within the polymer may not have the desired effect of reducing the cytotoxicity.…”

“…As a means of developing stronger adhesives, researchers have also functionalized these biological polymers with aldehyde groups that are capable to bond with amines in the tissue surface via a Schiff’s base reaction [41] [42] [43]. While aldehyde based bioadhesives demonstrate greater adhesive strength, they have been shown to elicit an inflammatory response from cells in contact with the adhesive [44] [45]. …”

Characterization of Star Adhesive Sealants Based On PEG/Dextran Hydrogels

“…[10] Aldehyde groups presented on these short carbon backbones create highly crosslinked tissue structures but do so while limiting their biocompatibility and potential for non-fixative applications. [11][12][13] Swellable PEG amine/dextran aldehyde composite materials are emerging as a controlled, biocompatible tissue adhesive. We explain how preservation of natural tissue amines provides biocompatibility for PEG/dextran that exceeds the stringent, destructive cyanide-based chemistry of cyanoacrylates, and adhere far better than fibrin glue.…”

Aldehyde‐Amine Chemistry Enables Modulated Biosealants with Tissue‐Specific Adhesion

“…Aldehydes in excess of what is required for cohesion or adhesion can induce tissue toxicity. [18] Consequently, material aldehyde density is the key design parameter for informative evaluation of tissue-material adhesion and tissue response. We designed and evaluated a series of PEG:dextran formulations featuring low (8.8%, abbreviated L-PD), medium (14.0%, abbreviated M-PD), and high (20.0%, abbreviated H-PD) levels of dextran aldehyde solid content.…”