Phorbol tumor-promoting component

Figure 1. General structure of the tumor-promoting component, phorbol, of croton oil. 12-O-tetradecanoyl-phorbol-l3-acetate (TPA) is the most potent promoter of the phorbol diesters. Phorbol didecanoate and phorbol dibenzoate, among others, have promoting ability but to a lesser extent than TPA. Phorbol alone has been reported to have no capacity to induce tumors as ODC.

Phorbol esters are tumor promoters capable of binding to and activating protein kinase C (PKC), one critical component in T cell activation.55,56 PMA is a structural analogue of diacylglycerol (DAG), an allosteric activator of PKC. PKC activation via phosphorylation leads to calcium release, resulting in a cascade of cellular responses including rapid proliferation.56 Experimentally, phorbol esters have been used as chemoattractants and to differentiate nonadherent monocytes to adherent macrophage cultures.55,57-60... 

Standard Reference Material (SRM) 1597 obtained from the National Institute of Standards and Technology, was tested in an assay of tumor initiation in female SENCAR mice (Marston et al. 2001). SRM 1597 is a mixture derived from a medium crude coke oven coal tar dissolved in toluene. Certified values have been published for selected PAH components of this mixture including B[a]P. Dibenzo[a,l]pyrene (DB[a,l]P) is not a component of SRM 1597. SRM 1597 (1 mg per 125 pL, which contains 10.4 pg B[a]P) was painted onto the shaved skin of 6-7-week-old mice over a period of 2 weeks (the number of applications was not reported) and in some cases, treatment with SRM 1597 was followed 5 minutes later with B[a]P or DB[a,l]P). The treatment groups were as follows 10 mice with 200 pL toluene as a control 30 mice with 1 mg SRM 1597 35 mice with 200 nm (50.4 pg) B[a]P in 100 pL toluene 35 mice with 1 mg SRM 1597 plus 200 nm (50.4 pg) B[a]P in 100 pL toluene 35 mice with 2 nmol (0.6 pg) DB[a,l]P and 35 mice with 1 mg SRM 1597 plus 2 nmol DB[a,l]P. Two weeks after initiation, twice-weekly promotion was begun with 12-0-tetradecanoyl-phorbol-13-acetate (TPA) at... 

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