Buu Hoi - Scientific Work - Chemical Carcinogenesis

Chemical Carcinogenesis

The overwhelming amount of Bửu Hội's contributions are in the field of chemical carcinogenesis and the synthesis of related organic chemical compounds. In the late 1940s and early 1950s, he had extensive collaborations with the quantum chemistry personnel of the Radium Institute on various aspects of the electronic theory of carcinogenesis. Bửu Hội was the first to propose the involvement of noncovalent forces. Together with Lacassagne and Rudali, in the 1940s he became the first to describe the phenomena of synergisma and antagonism between carcinogens. He demonstrated this by using hydrocarbons on the skin of mice and later extended this to hepatic and other carcinogens. Starting in 1947, he collaborated with Zajdela and Lacassagne in exploring the relationships between the structure and carcinogenic activity of polynuclear compounds. The study spanned a groundbreaking scale and depth.

These involved the fundamental ring systems and derivatives of 1,2-benzanthracene, the dibenzopyrenes, steranthrenes, anthanthrene, 1,2,3,4-dibenzanthracene, a variety of benzo and dibenzofluoranthenes. This was extended to large-molecular-size and "hypercondensed" hydrocarbons, ring opening and partial hydrogenation. During his study of dibenzopyrenes, he discovered a molecular arrangement involving the framework of aromatic hydrocarbons. His studies of the carcinogenic azulenophenalenes led him to question the role of aromaticity. Aside from his studies with aza-replaced hydrocarbons, benz- and dibenzacridines and –carbazoles, he also synthesised and tested a number of new structural types of heteroaromatics with reference to the nature, nuimber and position of the heteroatoms. These included the naphtho and benzo derivatives of pyridocarbazole and beta-carboline, heteroaromatics with sulfur, arsenic or selenium replacements. These were either alone or in association with nitrogen, as well as sulfur and nitrogen containing pseudoazulenes. A series of hydrocarbon-like polynuclear lactones were explored with the intent of establishing a connection between polynuclear aromatics and aflatoxins. Such studies of heteroatomic polynuclears led him to propose a "newer picture" of a carcinogenic hydrocarbon, helping the generalise the classical K-region hypothesis.

He contributed to studies on the carcinogenicity of 4-nitroquinoline-N-oxide derivatives, the production of plant tumors by a nitrosamine. He also studied metabolism and protein binding of polynuclears and the effect of the binding o DNA replication and transcription, testing the effect of various carcinogens on the hatching of shrimp eggs. From the mid 1960s onwards, Bửu Hội increasingly turned his focus to the structural facets of polynuclears which determine their ability to induce microsomal enzyme synthesis, in particular involving zoxazolamine and dicoumarol hydroxylation. Aside from his study of fundamental organic chemistry, chemical carcinogenesis and chemotherapy of leprosy and tuberculosis, Bửu Hội's team also conducted research into a wide range of issues of biological and therapeutic interest. These included the synthesis and testing anti-inflammatory non-steroid compounds, substituted sex hormones, anti-coagulant substances and their potentiation, antidiabetic agents, treatment of hypertension by methyl-DOPA, antioxidants and the chemophylaxy of aging and the toxicity of dioxine among others.