Abstract:The effects of the α-diketone derivatives 2,3-and 3,4-hexanediones were investigated in three non-neuronal cell lines (MCF7, HepG 2 and CaCo-2) as well as in the neuroblastoma line, SH-SY5Y. The MTT reduction assay was employed to determine the necrotic effects of the α-diketones and the neurotoxin 2,5-hexanedione over 4, 24 and 48 hr exposures. Flow cytometry was also used to study the effects of the three isomers on the cell cycle of the SH-SY5Y line only. With 2,5-hexanedione, the mean MTT IC 50 decreased more than 10-fold from 4 to 48 hr. The toxicities of both α-diketones were similar, with a more than 18-fold increase in sensitivity of the SH-SY5Y at 24 hr compared to that of 4 hr. With flow cytometry at 48 hr, SH-SY5Y apoptosis with 2,5-hexanedione rose throughout the concentration range evaluated (0-30 mM) while 2,3-and 3,4-hexanediones showed apoptosis over the concentration range 1-1.6 mM, with 3,4-hexanedione being the more potent compared to the 2,3-isomer. At 1.6 mM nearly all the cells had entered apoptosis in the presence of the 3,4-isomer, (94.9 ± 1.4%) but only 57.5 ± 4.1% of the 2,3-isomer-treated cells had reached that stage. The 2,3-and 3,4-isomers in diets alone may not pose a serious threat to human health. Further studies may be necessary to evaluate the effects of other dietary components on their toxicity. These α-diketones also display a degree of toxic selectivity towards neuroblastoma cells, which may have therapeutic implications.Hexanediones are formed biologically (2,5-hexanedione) as a result of exposure to the organic solvent hexane [1] and they also are present in the diet as food colourings and flavouring agents. 2,3-Hexanedione occurs naturally in beer, coffee and fermented soya beans and is used commercially to yield a buttery-cheesy taste in various foodstuffs and fragrances. 3,4-Hexanedione also occurs naturally in coffee, as well as cauliflower and it yields a sweet caramel-buttery odour and taste in butter, margarine and fruit flavourings [2]. The 2,5-isomer is an established human neurotoxin, which causes the cross-linking of neurofilaments; this process is linked to the onset of a polyneuropathy that is associated with occupational exposure to hexane [3,4]. In contrast, the 2,3-and 3,4-isomers have been generally viewed as non-toxic [2,5] although the 2,3-derivative induced mitotic chromosomal loss in the presence of an inducer of chromosomal malsegregation [6]. More recent studies have revealed the 2,3-and 3,4-isomers to be several fold more acutely toxic over 4 and 24 hr compared to the 2,5-isomer in a number of neural and astrocytic cell lines [7] and they are also capable of disrupting the cell cycle and causing apoptosis in the human SK-N-SH neuroblastoma cell line [8].To date, there have been no comparative studies aimed at determining if the 2,3-and 3,4-hexanediones illustrate any degree of specific toxicity towards neuroblastoma lines or are cytotoxic to human cell lines in general. Hence, the cytotoxicity of the three hexanedione derivatives was evalua...
