By that we mean it has paralyzed some investigators to think that mutagenesis, alone, can explain all of carcinogenesis. First, the definition of these two terms must be understood. Mutagenesis is that process that brings about a qualitative or quantitative alteration of the genetic information. An epigenetic process is that which alters the expression of the genetic information at the transcriptional, translational or posttranslational levels. While the role of mutations in the carcinogenic process appears well documented, the role of epigenetic events is not as well documented or as widely accepted.
Promotion is the mitogenic process that brings about the clonal expansion of initiated cells.
Also, the blockage of GJIC by the tumor promoters is reversible. These are not characteristics of a mutagen which acts in a random fashion on genes and is, for practical purposes, an irreversible event. One would never get a cancer if that were all that was needed. However, if in the first cell, a mutation occurred in a gene that prevented terminal differentiation but not proliferation, then one needs only to stimulate this initiated cell to proliferate a few times to produce a few million cells. At that time, the target size of cells with one hit increases the probability of a spontaneous mutation to occur in one of these cells.