ANEUPLOIDY CORRELATED 100-PERCENT WITH CHEMICAL TRANSFORMATION OF CHINESE-HAMSTER CELLS

Aneuploidy or chromosome imbalance is the most massive genetic abnorma lity of cancer cells. It used to be considered the cause of cancer whe n it was discovered more than 100 years ago. Since the discovery of th e gene, the aneuploidy hypothesis has lost ground to the hypothesis th at mutation of cellular genes causes cancer. According to this hypothe sis, cancers are diploid and aneuploidy is secondary or nonessential. Here we reexamine the aneuploidy hypothesis in view of the fact that n early all solid cancers are aneuploid, that many carcinogens are nonge notoxic, and that mutated genes from cancer cells do not transform dip loid human or animal cells. By regrouping the gene pool-as in speciati on-aneuploidy inevitably will alter many genetic programs. This geneti c revolution can explain the numerous unique properties of cancer cell s, such as invasiveness, dedifferentiation, distinct morphology, and s pecific surface antigens, much better than gene mutation, which is lim ited by the conservation of the existing chromosome structure. To dete rmine whether aneuploidy is a cause or a consequence of transformation , we have analyzed the chromosomes of Chinese hamster embryo (CHE) cel ls transformed in vitro. This system allows (i) detection of transform ation within 2 months and thus about 5 months sooner than carcinogenes is and (ii) the generation of many more transformants per cost than ca rcinogenesis. To minimize mutation of cellular genes, we have used non genotoxic carcinogens. It was found that 44 out of 44 colonies of CHE cells transformed by benz[a]pyrene, methylcholanthrene, dimethylbenzan thracene, and colcemid, or spontaneously were between 50 and 100% aneu ploid. Thus, aneuploidy originated with transformation. Two of two che mically transformed colonies tested were tumorigenic 2 months after in oculation into hamsters. The cells of transformed colonies were hetero geneous in chromosome number, consistent with the hypothesis that aneu ploidy can perpetually destabilize the chromosome number because it un balances the elements of the mitotic apparatus. Considering that all 4 4 transformed colonies analyzed were aneuploid, and the early associat ion between aneuploidy, transformation, and tumorigenicity, we conclud e that aneuploidy is the cause rather than a consequence of transforma tion.