Melvin Calvin (1974) - Carcinogenesis: Chemical, Physical and Biological

Melvin Calvin (1974)

Carcinogenesis: Chemical, Physical and Biological

Melvin Calvin (1974)

Carcinogenesis: Chemical, Physical and Biological

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Melvin Calvin received the unshared 1961 Nobel Prize in Chemistry for the elucidation of the so-called Calvin Cycle. The Calvin Cycle, which is in fact a cyclic sequence of enzymatically catalysed biochemical reactions, is part of the machinery that allows plants to turn sunlight into food. It explains in detail how plants convert aerial carbon dioxide into biomass. A process which is essential for sustaining life as we know it. In the present lecture, however, Calvin discusses a rather different topic: the development of cancer. In the early 1970s, he had established a group to work on this issue at the University of California at Berkeley. Here, Calvin explains how this group came into life and discusses some research efforts on-going at the time.He starts off by pointing out the special role of chemicals in cancer development. Already around 1775, it had been observed that chimney sweeps, whose task it was to clear ash and soot from chimneys, showed significantly increased rates of scrotum skin carcinoma. This disease can nowadays be linked to carcinogenic compounds, the so-called polycyclic aromatic hydrocarbons (PAHs), which are formed during combustion.At the time of Calvin’s talk, the involvement of PAHs in carcinogenesis was apparent, however, the precise mechanism was still speculative. It was believed that PAHs themselves were not carcinogenic, but were converted to carcinogenic epoxides only by enzymes of the body, the so-called aerial hydrocarbon hydroxylases. Still, as Calvin points out, the epoxides had never been detected in vivo and the biological consequences of their formation had not been identified. Calvin suggests that they might react with DNA, yielding a distortion of the helical DNA structure. He further discusses the proposition that such damage could have additional consequences if a viral infection occurred at the same time. The DNA repair mechanisms triggered by the body upon chemical-induced DNA damage could create a loophole for the insertion of viral DNA into the DNA of the host cell, according to Calvin. He concludes that viral and chemical factors might in fact “work together” towards carcinogenesis. Eventually, he presents the results of some early cancer-prevention experiments with drugs that block enzymes involved in the incorporation of viral DNA into host cell DNA. Calvin’s suggestions are based on quite a few assumptions, a fact which he was well aware of. During his talk, he thus adds a little disclaimer, stating that he has only half the data required to prove what he is proposing. However, according to Calvin, creativity in science is when you get the right answer despite not knowing everything you need to know. And, in fact, Calvin got most of his speculations right. Today we know that PAHs are converted to diol epoxides by the combined actions of cytochrome P and epoxide hydrolase enzymes. The diol epoxides may then react with cellular DNA. There is now also substantial evidence for a synergistic interaction of viral and chemical factors in carcinogenesis. A well-established example is the synergism between tobacco smoke (i.e. PAH intake) and human papilloma virus infection in the development of cervical cancer (cf. the Nobel Prize in Physiology or Medicine 2008 to Harald zur Hausen). Also, the prevention of cancer with certain enzyme-blocking drugs, as suggested by Calvin, is being followed up on. Friends of red wine might be pleased to read that, amongst others, resveratrol, a compound found in red grapes, can inhibit cytochrome P enzymes and thus potentially reduce the risk for cancer due to PAH intake [1]. [1] T. Shimada, Y. Fujii-Kuriyama, Cancer Science 95 (2004) 1.

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