Pathological and biochemical aspects of tumour promotion

Historically, the concept of tumour promotion was developed by Rous and Berenblum and their colleagues in the 1940's in order to explain their observations that wounding or painting the skin with the corrosive compound croton oil, although not carcinogenic per se nevertheless greatly increased the yield of skin tumours in mice which had been exposed previously to a low dose of the carcinogen, benzo[a]pyrene (BP)*. Some 15 years earlier, Dellman and his colleagues had noted the enhancing effect of wounding on the tumour yield in tar-painted or carcinogen-painted skin, but the potential importance of their work was largely overlooked both at the time and later. Berenblum described the effect of BP on the skin as 'initiation' of carcinogenesis and the enhancing effect of croton oil on tumour development as 'promotion'. Over the following 30 years, further work by Berenblum and his colleagues and by others, notably van Duuren, Boutwell and Hecker enabled many of the biological characteristics of two-stage carcinogenesis involving initiation and promotion to be defined in great detail, but always with a reference to the mouse skin model. Indeed, until quite recently, two-stage carcinogenesis involving initiation and promotion was thought to be a scientific oddity applicable only to the development of cancer in the mouse skin and to be of little relevance to the understanding of carcinogenesis in other organs. Now the pendulum has swung too far the other way, and almost any factor which enhances tumour incidence in any organ system in vivo is commonly called a promoter, even if it clearly fails (or has not been demonstrated) to conform to even the simplest operational requirements of a promoter as defined by Berenblum and his colleagues.