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Mutagens, carcinogens, and tumor promoters in our daily food

1982; Wiley; Volume: 49; Issue: 10 Linguagem: Inglês

10.1002/1097-0142(19820515)49

1097-0142

Takashi Sügimura,

Acute Lymphoblastic Leukemia research

H E IDEA that cancer cells arise from normal cellsT through somatic mutation has a long history, and was suggested as early as 1928 by B a ~e r .~ This idea is supported by the irreversibility of some cellular changes during carcinogenesis and the stability of most cancer phenotypes.I n 1957, Nakahara, Fukuoka and P6 showed that 4nitroquinoline 1 -oxide (4NQO) was carcinogenic when painted on mouse skin.4 N Q 0 was reported to be mutagenic towards Aspergillus in 1956.l"Moreover, treatment of lysogenized Escherichia coli with this compound resulted in phage induction.244 N Q 0 is reduced to 4-hydroxyaminoquinoline 1 -oxide (4HAQO) by enzymes in bacterial and mammalian cells with concomitant oxidation of reduced pyridine nucleotides.'"4HAQO has mutagenic activity2' and phage-inducing activity on lysogenic bacteria24 and can produce DNA strand scission in vitro.""Later Tada and Tada124 showed that 4HAQO can form an adducts with DNA bases in the presence of serine, ATP and seryl-tRNA synthetase.The seryl-4HAQO thus formed is thought to be an ultimate mutagen and carcinogen, and so 4HAQO can be regarded as a proximate carcinogen.Further metabolic reduction of 4HAQO yields biologically much less active 4-aminoquinoline 1 -oxide."'The metabolic pathway of 4 N Q 0 is showfi in Figure I .These findings in our laboratory and other laboratories in Japan prompted us to study the carcinogenicity of mutagens, the interaction of carcinogens with DNA, and the metabolism of carcinogens.In 1960, the strong mutagenicity of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was reported by Mandell and G r e e ~~b e r g .~~In 1966, we reported that on subcutaneous injection, MNNG induced transplantable fibrosarcomas in rats.'I7In the same year, Schoenthal'" and Druckrey and col-leagues22 also independently reported the carcinogenicity of this mutagen.After this discovery, a solution of MNNG was given to rats in their drinking water in our laboratory and found to produce adenocarcinomas of the glandular stomach (Fig. 2).'"9.'10On the basis of From the National Cancer Center Research Institute, Tsukiji, Chuo-