Chiu H. Wu

The action of transition metals on the genotoxicity of simple phenols, phenolic acids and cinnamic acids

Simple phenols (catechol, 4-methyl catechol, resorcinol, phloroglucinol and pyrogallol), phenolic acids (p-hydroxybenzoic acid, protocatechuic acid, vanillic acid, gallic acid, syringic acid and salicylic acid), a phenylacetic acid (3,4-dihydroxyphenylacetic acid) and eugenol were assayed for clastogenic activity in Chinese hamster ovary (CHO) cells with and without the addition of a n S9 mixture, Cu2+ (10-4M) and Mn2+ (10-4M). All dihydroxylated and trihydroxylated phenolics induced chromatid breaks and exchanges. The introduction of a methyl group seems to reduce the clastogenic capacity. The addition of an S9 mixture or the transition metals Cu2+ and Mn2+ enhanced the chromosome-damaging activity in some phenolics and suppressed it in others.

A comparative genotoxicity study of chlorogenic acid (3-O-caffeoylquinic acid)

Chlorogenic acid, a compound which occurs naturally in many food items, was assayed for genotoxic activity in 3 different test systems: reverse mutations in the preincubation test with Salmonella typhimurium, gene conversion with Saccharomyces cerevisiae strain D7, and chromosome aberrations in Chinese hamster ovary (CHO) cells. Chlorogenic acid was directly convertogenic and clastogenic, but lacked a mutagenic capacity in the Salmonella bioassay. The transition metal Mn2+ enhanced the clastogenic and convertogenic activity of chlorogenic acid. In the presence of Mn2+ (10(-4)M), chlorogenic acid increased the frequency of his+ revertants in TA98 and TA100 strains of S. typhimurium. Caffeic acid and, to a lesser degree, quinic acid, which are components of chlorogenic acid, also showed genotoxic activity. The results show the importance of using several assays in combination with transition metals when testing for genotoxicity.

Clastogenicity of furans found in food

Cultured Chinese hamster ovary (CHO) cells were exposed for 3 h to furan and 6 furan derivatives (furfural, furfuryl alcohol, 5-methyl furfural, 2-methyl furan, 2,5-dimethyl furan and 2-furyl methyl ketone). Each of the 6 furan derivatives induced a relatively high frequency of chromatid breaks and chromatid exchanges in the absence of a liver microsomal activation preparation. The response of the furans to the addition of an S9 mixture differed. The clastogenic activities of 5-methyl furfural, 2-furyl methyl ketone, furfural and furfuryl alcohol were increased, whereas that of 2-methyl furan and 2,5-dimethyl furan were significantly decreased. Furan itself showed a clastogenic activity only in the presence of an S9 mixture.

Induction of mitotic gene conversion by browning reaction products and its modulation by naturally occurring agents

Mitotic gene conversion in the D7 strain of Saccharomyces cerevisiae was significantly enhanced by exposure to non-enzymatic browning reaction products. These products were formed during the heating of sugar (caramelization reaction) or sugar-amino acid mixtures (Maillard reaction) at temperatures normally used during the cooking of food. Several modulating factors of this convertogenic activity were identified. These factors included two main groups: (1) trace metals which are widely distributed in the environment; and (2) several cellular enzymatic systems. The convertogenic activities of a heated glucose-lysine mixture and a commercial caramel powder were completely suppresses when yeast were concurrently exposed to these products and to either FeIII or CuII. Equimolar concentrations of MnII or sodium selenite had no effect on the convertogenic activity of the products of either model system. Horse-radish peroxidase, beef liver catalase and rat liver S9 preparations each decreased the frequency of gene conversion induced by the caramel powder and the heated glucose-lysine products. This modulating activity of the enzymes was lost if they were heat-inactivated. These studies indicate the presence of a variety of protective mechanisms which can modify genotoxic components in complex food mixtures.

Clastogenic activity of dried fruits

The clastogenic activities of several commercially-dried fruits, including black and golden-seedless raisins, medium-sized California prunes, table dates, bananas, California black mission figs and breakfast apricots, were examined using Chinese hamster ovary (CHO) cells as the test organism and chromosome aberrations as the endpoint. Treatment of the CHO cells with water extracts of these dried fruits significantly increased the frequencies of metaphase plates with 1 chromosome break or exchange as well as the average number of chromosome exchanges per metaphase plate. A liver microsomal S9 mixture reduced this clastogenic activity. Dried fruits represent an example of widely consumed food products with strong genotoxic activities.