Mechanism of Carcinogenesis by Polycyclic Aromatic Hydrocarbons: Aneuploidy precedes malignant transformation and occurs in all cancers

摘要

Despite over Ioo years of cancer research, including huge investments in the last decades to find cancer-specific mutations, the genetic causes of most cancers are still unclear. Over Ioo cancer-specific mutations have been idntified (Bishop, 1995; Mitelman et al., 1997; Haber & Fearon, 1998), but there is as yet no functional proof that any one of these mutations or a combination of them causes cancer (Duesberg, 1995; Lijinsky, 1989). The challenge is to explain the complex and heterogenous phenotypes of cancer cells (Hansemann, 1890; Heim & Mitelman, 1995), and the very slow and inefficient mechanism of carcinogenesis (Cairns, 1978). Cancer-specific phenotypes include (i) abnormal growth rates, (ii) metabolism, (iii) morphology nad composition; (iv) neogantigens not expressed in the tissue of origin; (v) dedifferential tion or anaplasis (Hansemann, 1890); (vi) progression of malignancy generating invasiveness and metastasis; (vii) abnormally high numbers of centrosomes, i.e. over 2 (brinkley & Goepfert, 1998); and (viii) genetic or karyotypic instability, generating polymorphism of all of these properties among the cells of the same cancers (Hansemann, 1890; Winge, 1930; Hauschka, 1961; Nowell, 1976; Heppner & Miller, 1998), despite their clonal origin (Cairns, 1978; Heim & Mitelman, 1995; Nowell, 1976).