FROM THE COAL-TAR CANCER OF YAMAGIWA TO HEILICOBACTOR - ASSOCIATED GASTRIC CANCER: OCCUPATIONAL, DAILY LIFE-STYLE AND INFECTION / INFLAMMATION - RELATED CARCINOGENESIS
MASAAKI TERADA
In Tokyo, Yamagiwa first succeeded in inducing skin cancers on rabbit ears by repeated painting of coal-tar in 1915. Sasaki and Yoshida subsequently produced hepatomas in rats by feeding an azo-dye, these being equivalent to human occupational cancer due to heavy exposure to a single or a limited number of carcinogenic factor(s). 4-Nitroquinoline 1-oxide, a mutagen was proven to be carcinogenic in 1957 (Nakahara). The well-established multiple step nature of carcinogenesis is linked to the occurrence of multiple genetic alterations. Humans are continuously exposed to various kinds of mutagenic xenobiotics each at low levels, good examples being the relatively recent identified series of heterocyclic amines present in some cooked foodstuffs (Sugimura et al.). We are also exposed to genetoxic autobiotics, often generated by inflammation and infection and a contribution of active oxygen species has been demonstrated, for example regarding 8-OH-guanine adduct formation and related repair (Nishimura and Sekiguchi). An awareness of the importance of viruses goes as far back as 1914 when Fujinami revealed the existence of a chicken sarcoma virus. The finding of the ts mutant of the Rous sarcoma virus was a mile-stone in generation of information on functions of oncogene products (Toyoshima, 1969). The first example of a concrete link between virus and human cancer was provided by Takatsuki, Hinuma, Miyoshi and Yoshida, working an adult-T cell leukemia and integration of the HTLV-I genome into T-cell chromosomes. AML-1, the most frequent target gene of chromosome translocation found in human leukemia is a more recently discovered example, arising from the human genome project (Ohki). It is now also well established that bacterial infection can be a major risk factor and eradication of Helicobacter pylori has been found to lead to regression of some MALT. Proof of a causative role was provided by the generation of stomach cancers by combined treatment with Helicobacter pylori and MNNG in Mongolian gerbils. Twelve points for cancer prevention, based on life style improvement, were previously proposed by the National Cancer Center, including balanced dietary habits. These are in agreement with the 15 points for cancer prevention recently issued by American Institute for Cancer Research. Japan encourages early diagnosis by means of mass-screening and treatment of early stage cancer. Collaborations between academia and industry yielded new diagnostic tools for image analyses, such as Fuji-Computed Radiography (FCR) and Toshiba-Helical CT and others. The encouragement of fundamental research has yielded various fruits, with important advance in areas such as cadherin biology (Takeichi), IL-6 (Kishimoto), IRF (Taniguchi), FAS (Nagata) and others.