Flavonoids, such as quercetin and kaempferol, and their glycosides, are widely distributed in vegetables and fruits. Sugimura, T. et al. investigated the mutagenicity of flavone derivatives, and found that quercetin and kaempferol showed high mutagenic activities in Salmonella typhimurium TA98 with S9 mix, comparable to that of the typical carcinogen, benzo[a]pyrene. These novel findings were published in Proc. Jpn. Acad. Ser. B 53, 194-197, 1977. Other research groups also reported the mutagenic properties of flavone derivatives in S. typhimurium strains. These observations led to the commencement of long-term animal carcinogenesis experiments involving quercetin. A USA-Turkey joint study reported that feeding rats with 0.1% quercetin in the diet produced carcinomas. However, Japanese scientists showed no carcinogenicity with quercetin in rats, mice, or hamsters, even at 10% in the diet. NTP Technical Report on the Toxicology and Carcinogenesis Studies of Quercetin in F344/N Rats concluded that there was no evidence of its carcinogenic activity. Therefore, the potential risk of quercetin in human cancers is likely to be negligible. These flavonoid issues provided a warning regarding the simplistic understanding that mutagens are carcinogens, and microbial tests alone are inadequate for safety assessment; therefore, and a battery of tests for genotoxicity is recommended. Thus, the informative report in 1977 made significant contributions to initiating and promoting genotoxicity studies of flavonoids.

Lifestyle, especially diet, significantly impacts cancer development. Sugimura, T. et al. discovered that grilled fish smoke and charred parts are highly mutagenic in Salmonella typhimurium. They identified two novel mutagenic heterocyclic amines (HCAs), 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) and its derivative, Trp-P-2, from tryptophan pyrolysate. Published in Proc. Jpn. Acad. (53, 58-61, 1977), their findings initiated the identification of over 10 mutagenic HCAs in cooked foods, most of them newly registered. These 10 HCAs were demonstrated to induce cancers in organs including the liver, colon, breast, and prostate in mice and rats. HCAs are metabolized primarily by CYP1A2 to hydroxyamino derivatives. Their ester forms then adduct at guanine bases, altering genes such as Apc and β-catenin. Quantification of HCAs in cooked foods and human samples, along with epidemiological observations, suggests HCAs likely contribute to human cancers.

In the world history of cancer research, three achievements in Japan were groundbreaking. First, in 1915, Katsusaburo Yamagiwa and Koichi Ichikawa induced skin cancer on the ears of rabbits by the repeated application of coal tar. This achievement was the world’s first generation of artificial cancers in experimental animals. Second, in 1932, Takaoki Sasaki and Tomizo Yoshida observed liver cancer in rats fed on rice inoculated with ortho(o)-aminoazotoluene. This achievement was the first ever artificial cancer in the internal organs of experimental animals. Third, in 1967, Takashi Sugimura gave N-methyl-N′-nitro-N-nitrosoguanidine, a known chemical mutagen, to mice in drinking water and induced stomach cancer. This achievement was the first artificial production of stomach cancer and provided experimental evidence that cancer is a disease originated from DNA abnormalies. In commemoration of the publication of the 100th volume of the Proceedings of Japan Academy, Series B, from articles previously published in the Proceedings, two papers related to the achievements of Takaoki Sasaki have been selected and republished with this article.

Biomimetic molecular designs can yield superior biomaterials. Polymers with a phosphorylcholine group, a polar group of phospholipid molecules, are particularly interesting. A methacrylate monomer, 2-methacryloyloxyethyl phosphorylcholine (MPC), was developed using efficient synthetic reactions and purification techniques. This process has been applied in industrial production to supply MPC globally. Polymers with various structures can be readily synthesized using MPC and their properties have been studied. The MPC polymer surface has a highly hydrated structure in biological conditions, leading to the prevention of adsorption of proteins and lipid molecules, adhesion of cells, and inhibition of bacterial adhesion and biofilm formation. Additionally, it provides an extremely lubricious surface. MPC polymers are used in various applications and can be stably immobilized on material surfaces such as metals and ceramics and polymers such as elastomers. They are also stable under sterilization and in vivo conditions. This makes them ideal for application in the surface treatment of various medical devices, including artificial organs, implanted in humans.

Λ^＊ = Λ(1405) plays an essential role in the formation of kaonic nuclear clusters (KNC). The simplest KNC, K^－pp, has the structure Λ^＊p = (K^－p)^I=0p, in which a real kaon migrates between two nucleons, mediating super-strong Λ^＊p attraction. Production data of K^－pp have been accumulated by DISTO, J-PARC E27 and J-PARC E15 experiments. For K^－K^－pp the attractive covalent bond of Λ^＊Λ^＊ is doubly enhanced compared to the Λ^＊p one. Consequently, Λ^＊ multiplet, (Λ^＊)_m, with m(m－1)/2 bonds becomes more stable than its corresponding neutron aggregate, (n)_m, at m = 8－12, suggesting the possible existence of stable Λ^＊ matter. A long-lived strangelet of (Λ^＊)_m=6 is presumed as a precursor. The production of K^－K^－pp by high-energy pp or heavy-ion collisions is awaited as a doorway to so-far unknown Λ^＊ matter.