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Tumour promoters of the irritant diterpene ester type as risk factors of cancer in man

Botanical journal of the Linnean Society 1987 v.94 no.1-2 pp. 197-219
Croton, Human herpesvirus 4, Thymelaeaceae, Vernicia fordii, carcinogenesis, carcinogenicity, carcinoma, drugs, esters, etiology, humans, pharmacokinetics, polycyclic aromatic hydrocarbons, raw materials, risk, risk factors, viruses, China
Tumour promoters of the irritant diterpene ester type as risk factors of cancer in man. It is widely accepted in experimental and epidemiologic oncology that in real human life multifactorial causation of cancer is the rule and classical unifactorial causation the exception. This current and comprehensive concept of the aetiology of cancer has evolved essentially from in-depth investigations of tumour promoters of the irritant DTE type, found occurring in the Euphorbiales (Euphorbiaceae, Thymelaeaceae) in about the last 20 years. Moreover, the irritant DTEs are most powerful tools in experimental cell and cancer research, as illustrated by current results of investigations of their toxicokinetics and toxicodynamics. Quantitative chemical and toxicologic investigations indicate that life-style oesophageal cancer, prevalent on Curasao, is the first case of cocarcinogens of the DTE type (‘Welensalifactors' from Croton flavens L.) shown to be the principal risk factor in a multifactorial human cancer, in conjunction with initiators of the solitary carcinogenic PAH type. The typical tigliane type DTE Welensalifactor F, was isolated, also from the tung oil tree (Aleuritesfordii). It was shown that DTEs of the tigliane, ingenane and daphnane types activate certain human tumour viruses, e.g. the Epstein-Barr virus. The latter virus is known to be associated with nasopharyngeal carcinoma (NPC) prevalent in South China. It is concluded that uncontrolled utilization of Euphorbiaceae-derived materials, e.g. as (ethno-medicinal) drugs, or as technological raw materials, may be responsible for high incidence rates of certain human cancers due to DTE type risk factors of the promoter type. The identification of well defined cocarcinogens of the DTE type as a new, non-classical group of risk factors in terms of ‘per se essentially non-carcinogenic amplifiers' of carcinogenesis adds a new dimension to the aetiology of cancer in man. Together with the multifactorial concept of carcinogenesis, it may allow a more refined assessment of the cancer risk.