what is a tumor initiator and a tumor promoter?

Answer 1

A concern regarding repetitive exposure is that for relatively weak carcinogens it is possible that the power of the assay (i.e., number of animals at risk per dose per unit of time) is inadequate to show a single dose/exposure effect. However, the combined results of over 400 bioassays conducted by the National Toxicology Program (NTP) show that exposures to a maximum tolerated dose (MTD) of the chemical for over two-thirds of the animal's life span is needed for even DNA reactive agents.

If repetitive exposures are required to manifest the carcinogenic potential of substances, the distinction between TUMOR INITIATOR AND TUMOR PROMOTER becomes problematic. The action of the initiator appears to potentiate the tumor induction process through the induction of mutations in appropriate target cells, which are then provided with a proliferative stimulus by the actions of the promoter. In conventional bioassays the capacity of an initiator to also promote the proliferation of initiated cells may be somewhat less, but it is still effective when exposures are repeated. The non-DNA reactive carcinogen or promoter may, conversely, be less efficient in creating cells that can be promoted into tumor development. Repetitive exposure to a promoter alone may result in mutations via indirect oxidative pathways or changes in gene regulation that provide cells with a proliferative advantage. The initiation step in the two-stage model thus potentiates the neoplastic process, which then develops over a period of many weeks upon repetitive exposure to the promoter, whereas the equivalent process in conventional bioassays requires a period of many months or years to develop. - for further details see - http://www.ehponline.org/docs/1999/107-8/editorial.html