Abstract：
:Human populations are exposed to complex environmental mixtures of acrolein, methylvinyl ketone (MVK) and other type-2 alkenes. Many members of this chemical class are electrophiles that possess a common molecular mechanism of toxicity; i.e., protein inactivation via formation of stable cysteine adducts. Therefore, acute or chronic exposure to type-2 alkene mixtures could represent a health risk due to additive or synergistic interactions among component chemicals. Despite this risk, there is little experimental information regarding the joint effects of type-2 alkenes. In the present study we used sum of toxic units (TUsum = ∑TUi) to assess the relative toxicity of different type-2 alkene mixtures. These studies involved well characterized environmental type-2 alkene toxicants and included amide (acrylamide; ACR), ketone (methyl vinyl ketone; MVK), aldehyde (2-ethylacrolein; EA) and ester (methyl acrylate; MA) derivatives. In chemico analyses revealed that both binary and ternary mixtures could deplete thiol groups according to an additive joint effect at equitoxic and non-equitoxic ratios; i.e., TUsum = 1.0 ± 0.20. In contrast, analyses of joint effects in SNB19 cell cultures indicated that different permutations of type-2 alkene mixtures produced mostly synergistic joint effects with respect to cell lethality; i.e., TUsum < 0.80. A mixture of ACR and MA was shown to produce joint toxicity in a rat model. This mixture accelerated the onset and development of neurotoxicity relative to the effects of the individual toxicants. Synergistic effects in biological models might occur when different cellular proteomes are targeted, whereas additive effects develop when the mixtures encompasses a similar proteome.
journal_name
Chem Biol Interactjournal_title
Chemico-biological interactionsauthors
Zhang L,Geohagen BC,Gavin T,LoPachin RMdoi
10.1016/j.cbi.2016.06.014subject
Has Abstractpub_date
2016-07-25 00:00:00pages
198-206eissn
0009-2797issn
1872-7786pii
S0009-2797(16)30230-7journal_volume
254pub_type
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