Table 8.

Genotoxicity of cis‐2‐Butene‐1,4‐dial (BDA) in vitro

Test system	Experimental system	Concentration/treatment	Result	Comments	Reference
Formation of ICLs	In situ oxidation of furan containing oligonucleotide		Positive: formation of DNA interstrand cross‐link in duplex oligonucleotides	–	Halila et al. (2005)
Formation of dC and dA adducts	Calf thymus DNA and DNA from BDA‐treated S. Typhimurium TA104		Positive: formation of DNA adducts in both systems	–	Byrns et al. (2006)
Bacterial reverse mutation assay (Ames test)	S. Typhimurium TA104	118, 143, 177, 244, 362 μg/plate	Positive	Toxic at doses > 177 μg/plate BDA mutagenic potential revealed in a specific strain sensitive to aldehydes	Peterson et al. (2000)
SSBs and crosslinks by alkaline elution	CHO‐K1	14, 42, 126 μg/mL	Positive: both end‐points	High concentrations (in the mM range) but no apparent toxicity	Marinari et al. (1984)
Forward mutation Comet and micronucleus assays	L5178Y tk+/− mouse lymphoma cells	0.5, 1.1, 2.1, 4.2 μg/mL	Positive: Comet and mutation (at ≥ 70% survival) Negative: micronucleus assays and crosslinks	–	Kellert et al. (2008a)
Mutation induction at the cII transgene	In vitro treatment of mouse embryo fibroblasts from Big Blue B6C3F1 mice	0.2 and 0.4 μg/mL	Negative: no increase in mutation frequency Positive::change in mutational spectrum	Increase in AT > CG transversions	Terrell et al. (2014)

BDA: cis‐but‐2‐ene‐1,4‐dialdehyde; CHO: Chinese hamster ovary; dA: 2’‐deoxyadenosine; dC: 2’‐deoxycytidine; dG: 2’‐deoxyguanosine; SSB: single strand break; ICL: inter‐strand crosslink.