Mutagenicity caffeine

Palitti, F. Becchetti, A. (1977) Effect of caffeine on sister chromatid exchanges and chromosomal aberrations induced by mutagens in Chinese hamster cells. Mutat. Res., 45, 157-159... 

GOODGAL Scientists have the responsibility not to raise issues that are not based on fact. If it is demonstrated that caffeine is a mutagenic agent in a large variety of organisms, and under a variety of conditions, or if one can at least define them, then I think there is a much more solid basis for raising this issue. My own feeling is that there has been too much said today on too few facts. 

CYP1A2 Silent base More inducible Caffeine, activates food mutagens Uncertain... 

Caffeine has been found to be weakly mutagenic in some nonmammalian animal models. It is not been found to be mutagenic in Ames Salmonella assays. 

Coffee brewed from roasted beans and those prepared from instant powder, including the caffeine-free type, all display mutagenic activity. Apart from natural mutagens such as caffeic acid and its precursors chlorogenic and neochlorogenic acids, these drinks contain mutagenic products of pyrolysis methylglyoxal and less active gly-oxal and diacetyl (Ames, 1986) ... 

These pyrolysis products were also found in roasted tea and brandy-type alcoholic beverages (Sugimura and Sato, 1983). In addition, as a result of ethanol metabolism, mutagenic acetaldehyde is formed, while in coffee and tea caffeine, an inhibitor of DNA repair synthesis is present and may also contribute to cancer risk. 

Adamson R. (2000) Evaluation of coffee and caffeine for mutagenic, carcinogenic, and anticarcinogenic activity. Am. Chem. Soc. Symp Ser. (Caffeinated Beverages), 754, 71-77. 

Clarke, C. R. and Wade, M. J., Evidence that caffeine, 8-methoxypsoralen and steroidal diamines are frameshift mutagens for E. coli K-12. Mutation Res. 28 123-125 (1975). 

Some substances induce a depurinization and depyrimidinization of DNA chains, thus making the DNA deoxyribosephosphate skeleton labile with a subsequent depolymerization of the molecule. The partial DNA depolymerization can also result from an inhibition of the repair of single-chain breaks in DNA, which results in chromosomal breaks. This mechanism of the action is assumed to be the case with caffeine, whose mutagenic effect was observed in mammal cells [3]. 

Weisburger JH, Dolan L, Pittman B. Inhibition of PhIP mutagenicity by caffeine, lycopene, daidzein, and genistein. Mutat Res 1998 416 125-128. 

The mutagenic effect of caffeine was detected in 1948 independently by Fries and Kihlman (1948) and by Witkin (quoted by Demerec, 1949), using as experimental materials the fungus Ophiostoma multiannulatum and the bacterium Escherichia coli respectively. The chromosome-breaking effect of caffeine was demonstrated in plants by Kihlman and Levan (1949) and in mammalian cells by Ostertag et aL (1965). 

The parent compound, coumarin, has been found to cause chromosome breakage in animal tissues [207, 336]. The mechanism of this action and the effect on chromosomes by chemical mutagens has not yet been elucidated [337], There is hardly any structural relationship of action between these compounds. Good chromosome breakers of mammalian cells or plants include bromouracil, caffein and derivatives, alkylating agents, phenols, quinones, colchicine, methyl-phenyl-nitrosamine [337-343]. However, there is another plant product, podophyl-lotoxin, related to coumarin, which also causes chemical mutagenesis [338, 344]. 

Onfelt A, Jenssen D (1982) Enhanced mutagenic response of MNU by posttreatment with methylmercury, caffeine or thymidine in V79 Chinese hamster cells. Mutat Res 106 297-303... 

Caffeine appears to be a weak mutagen in some nonmammalian systems. But its significance as a mutagen in humans is unknown. It is noteworthy, however, that studies of the caffeine intake of pregnant women have shown no association between caffeine and birth defects. 

Aqueous extracts of guarana were found to be genotoxic and mutagenic when tested in Escherichia coli and Salmonella typhi-murium. The effect was attributed to the formation of a toxic caffeine/catechin complex. ... 

In 1948, Fries and Kihlman in Sweden reported the production of auxotrophic mutations in the ascomycete Ophiostoma multiannulatum by prolonged immersion of the conidia in solutions of caffeine (0.2%) or theophylline (0.6%). Either treatment yielded about 1% auxotrophs at survival levels of about 0.2% control mutation frequencies were very low. Qualitatively, the results were especially interesting because they showed a difference between the mutational spectra induced by these two purines on the one hand and X-irradiation on the other. This was most striking for inositol requirers, which formed less than 5% of radiation-induced auxotrophs but more than 40% of purine-induced ones. This is one of the rare cases of mutagen specificity for a whole locus or biochemical pathway. Like similar cases that were subsequently reported from the same laboratory, it may rest on selective effects of the plating medium, amplified by the previous treatment of the plated conidia. 

I. D. Adler, Cytogenetic investigations of mutagenic action of caffeine in premeiotic... 

I. D. Adler, The problem of caffeine mutagenicity, in Chemical Mutagenesis in Mammals and Man (F. Vogel and G. Rohrborn, eds.) pp. 383-403, Springer-Verlag, Berlin, Heidelberg, New York (1970). 

W. Ostertag and J. Haake, The mutagenicity in Drosophila melanogaster of caffeine and of other compounds which produce chromosome breakage in human cell in culture, Z Vererbungsl. 98, 299-308 (1966). 

B. A. Kihlman, G. Odmark, S. Sturelid, and K. Norlen, The relationship between intracellular ATP concentration and the frequency of chromatid aberrations induced by caffeine and 8-ethoxycaffeine in plant root tips and in cell cultures of the Chinese hamster, European Environmental Mutagen Society, Abstracts, First Annual Meeting (May 5-7, 1971), Noordwijkerhout, The Netherlands (1971). 

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