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

Abstract

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.

Dietary cancer risk from conditional cancerogens (tumor promoters) in produce of livestock fed on species of spurge ( Euphorbiaceae )

“…In previous studies, however (FuÈ rstenberger and Hecker 1985), 12,13-diesters of 4-deoxyphorbol (2) potentially exhibited tumor-promoting activities. Euphorbia factors Nu4 and Nu2, as 12,13±20-triesters of 4-deoxyphorbol (2), represent the structural type of`c ryptic'' tumor promoters i.e., diterpene esters required to be activated metabolically to become tumor promoters (for the``cryptic principles'' of DTE see, for example, Wiriyachitra et al 1985;Hecker 1987).…”

Dietary cancer risk from conditional cancerogens in produce of livestock fed on species of spurge ( Euphorbiaceae )

“…In this case they display their promoting activity in conjunction with initiators or solitary cancerogens of the polycyclic aromatic hydrocarbon type (Hecker et al 1983, Hecker 1987a. Tumor promoters, speci®cally of the diterpene ester type, may be classi®ed as second order risk factors of cancer (Hecker 1990).…”

Tumour promoter activity in Malaysian Euphorbiaceae

“…A similar study also indicated a causal link between the regular intake of phorbol esters contained in 'Walensalii tea' prepared from Crotonflaven L. (Euphorbiaceae) and the high incidence of oesophageal cancer in Curacao Island of the Caribbean (Hecker, 1987).…”