Cysteine containing chewing gum for the prevention of upper digestive tract cancers?

Researchers at the University of Helsinki, Finland, suggest that cysteine containing tablets and chewing gum can be a new way for the prevention of upper digestive tract cancers.

It has been estimated that in developed countries up to 80 % of the cancers of mouth, pharynx and oesophagus are caused by smoking and alcohol drinking. According Finnish researchers these epidemiological findings can at least in part be explained by the fact that alcohol drinking and smoking result in a strong local exposure of the upper digestive tract to acetaldehyde, and they have proved that acetaldehyde exposure can be markedly prevented by a tablet that releases amino acid, l-cysteine.

The research group of professor Mikko Salaspuro, University of Helsinki and Helsinki University Hospital, Finland, published already in 1990s a hypothesis, that microbes representing normal human digestive tract flora produce locally acetaldehyde from ethanol and that this may expose them for an increased risk of digestive tract cancers.

The hypothesis was strongly supported by Japanese studies showing that digestive tract cancer risk is markedly increased in Japanese drinkers, who have a decreased ability to remove acetaldehyde because of a gene mutation. The cause and effect relationship was subsequently strongly supported by a novel finding of the Finnish research group showing that after a small dose of alcohol Asians with the above mentioned gene mutation have 2-3 times higher concentrations of acetaldehyde in their saliva than those with the normal acetaldehyde removing enzyme. Most recently, a research group from NIH reported a mechanism that induces DNA-damage in those acetaldehyde concentrations that are found in the saliva after drinking of alcohol.

It has been known already for decades that a harmless aminoacid l-cysteine is able to bind effectively acetaldehyde and thereby eliminate its toxicity. On this basis professor Salaspuro and professor Martti Marvola, University of Helsinki, started to develop l-cysteine containing and acetaldehyde eliminating preparations that eventually could be used for the prevention of digestive tract cancers. The first two preparations were slowly l-cysteine releasing tablets that effectively eliminated acetaldehyde derived to the mouth and saliva either after a challenge of alcohol or during smoking.

The methods developed by the research groups of Salaspuro and Marvola have been patented world wide. The owner of the patents is nowadays Finnish company Biohit Oyj. The first commercial product based on this patented method is l-cysteine containing chewing gum that was launched on the market in the 11th International Congress of Oral Cancer on May 14-17, in Italy.

"We know that with this chewing gum it is possible to eliminate acetaldehyde totally from the saliva during smoking. We do hope that this will in the future turn out to be a novel method for the prevention of alcohol and tobacco smoking associated oral cancers. However, long term randomised controlled trials are naturally needed before the possible cancer preventive effects can be proved. We are currently planning that type of studies", says Salaspuro.

With the saliva carcinogenic acetaldehyde is distributed after swallowing to the pharynx, oesophagus and stomach. Consequently, the effects of l-cysteine may extend to the whole upper digestive tract area. On the other hand, carcinogenic acetaldehyde can be produced also endogenously by the oral microbes from various foodstuffs with high sugar or carbohydrate content, especially in an achlorhydric stomach. Atrophic gastritis and achlorhydria are well known risk factors of gastric cancer. Therefore, in addition to the chewing gum, also other cysteine containing preparations are under development. The goal is to develop new products releasing slowly cysteine in different parts of the gastrointestinal tract by which acetaldehyde can be eliminated not only in the mouth but also in the stomach and may be also in the large intestine.

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Further information:
Professor Mikko Salaspuro, MD, Ph.D.
+358-500-511 689
mikko.salaspuro@hus.fi

Professor Martti Marvola, Ph.D. (Pharm.)
+358-50-545 4599
martti.marvola@helsinki.fi

References:

Salaspuro V, Hietala J, Kaihovaara P, Pihlajarinne L, Marvola M, Salaspuro M. Removal of acetaldehyde from saliva by a slow-release buccal tablet of l-cysteine. Int J Cancer 97:361-364.

Salaspuro V, Hietala J, Marvola M, Salaspuro M. Eliminating carcinogenic acetaldehyde by cysteine from saliva during smoking. Cancer Epid Biomarkers Prev 2006;15:146-149.

Theravathu JA,. Jarunga P, Nath RG, Dizdarogly M, Brooks PJ. Polyamines stimulate the formation of mutagenic 1,N2-propanodeoxyguanosine adducts from acetaldehyde. Nucleic Acids Res 2005;33:3513-3520.

Väkeväinen S, Tillonen J, Agarwall DP, Srivastava N, Salaspuro M. High salivary acetaldehyde levels after a moderate dose of alcohol in ALDH2-deficient subjects: strong evidence for the local carcinogenic action of acetaldehyde. Alcohol Clin Exp Res 2000;24:873-877.

Väkeväinen S, Mentula S, Nuutinen H, Salmela KS, Jousimies-Somer H, Färkkilä M, Salaspuro M. Ethanol-derived microbial production of carcinogenic acetaldehyde in achlorhydric atrophic gastritis. Scand J Gastroenterol 2002;37;648-655.

Yokoyama A, Muramatsu T, Ohmori T, Yokoyama T, Okoyama K, Takaqhashi H, Hasegawa Y, Higuchi S, Mauyama K, Shirakura K, Ishii H. Alcohol-related cancers and aldehyde dehydrogenase-2 in Japanese alcoholics. Carcinogenesis 1998;19:1383-1387.


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