Das Krebsproblem

Bauer, Karl-Heinrich

doi:10.1007/978-3-642-86062-1

Cited by 280 publications

(30 citation statements)

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“…16,21,116 and animal experiments, beginning with Yamagiwa and Ishikawa in 1915, 46 have shown long ago that carcinogens cause cancer only after long neoplastic latencies of many months to decades, but the reason for the inevitable latencies remained unsolved. 2,16,18,20,21,46,[116][117][118] Neoplastic latenies setting apart initiation by carcinogens and cancer. More recent research has revealed that carcinogens induce random aneuploidy without delay, but cancers with clonal karyotypes only after long delays, as predicted by the speciation theory.…”

Section: Figurementioning

confidence: 99%

Is carcinogenesis a form of speciation?

Duesberg

Mandrioli²,

McCormack³

et al. 2011

Cell Cycle

113

138

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Section: Figurementioning

confidence: 99%

Is carcinogenesis a form of speciation?

Duesberg

Mandrioli²,

McCormack³

et al. 2011

Cell Cycle

113

138

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“…Aneuploidies are not heritable, because they corrupt embryogenic developmental programs [113,114], which is usually fatal [157,191] as originally shown by Boveri [142]. Only some very minor congenital aneuploidies, such as Down syndrome and syndromes based on abnormal numbers of sex chromosomes, are sometimes viable, but only at the cost of severe physiological abnormalities and of no or very low fertility [31,65,68,192]. Thus, ontogenesis is nature's checkpoint for normal karyotypes.…”

Section: Cancer Is Not Heritablementioning

confidence: 99%

Aneuploidy and Cancer: From Correlation to Causation

Duesberg

Fabarius³

et al. 2006

Infection and Inflammation: Impacts on Oncogenesis

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Conventional genetic theories have failed to explain why cancer (1) is not found in newborns and thus not heritable; (2) develops only years to decades after 'initiation' by carcinogens; (3) is caused by non-mutagenic carcinogens; (4) is chromosomally and phenotypically 'unstable'; (5) carries cancer-specific aneuploidies; (6) evolves polygenic phenotypes; (7) nonselective phenotypes such as multidrug resistance, metastasis or affinity for non-native sites and 'immortality' that is not necessary for tumorigenesis; (8) contains no carcinogenic mutations. We propose instead that cancer is a chromosomal disease: Accordingly, carcinogens initiate chromosomal evolutions via unspecific aneuploidies. By unbalancing thousands of genes aneuploidy corrupts teams of proteins that segregate, synthesize and repair chromosomes. Aneuploidy is thus a steady source of karyotypic-phenotypic variations from which, in classical Darwinian terms, selection of cancer-specific aneuploidies encourages the evolution and subsequent malignant 'progressions' of cancer cells. The rates of these variations are proportional to the degrees of aneuploidy, and can exceed conventional mutation by 4-7 orders of magnitude. This makes cancer cells new cell 'species' with distinct, but unstable karyotypes, rather than mutant cells. The cancer-specific aneuploidies generate complex, malignant phenotypes, through the abnormal dosages of the thousands of genes, just as trisomy 21 generates Down syndrome. Thus cancer is a chromosomal rather than a genetic disease. The chromosomal theory explains (1) nonheritability of cancer, because aneuploidy is not heritable; (2) long 'neoplastic latencies' by the low probability of evolving competitive new species; (3) nonselective phenotypes via genes hitchhiking on selective chromosomes, and (4) 'immortality', because chromosomal variations neutralize negative mutations and adapt to inhibitory conditions much faster than conventional mutation. Based on this article a similar one, entitled 'The chromosomal basis of cancer', has since been published by us in Cellular Oncology 2005;27:293-318. Copyright © 2006 S. Karger AG, Basel Despite over 100 years of cancer research, the cause of cancer is still a matter of debate . We propose here that the problem of cancer is still

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“…Even the cells of a given "clonal" cancer proved to be heterogeneous with regard to chromosome numbers (4,6,9,100). Moreover, several investigators have claimed diploid cancers (15,17,93,100). In view of this, aneuploidy has been interpreted either as a "Folgeerscheinung" (consequence) (15) that is not essential for carcinogensis (16)(17)(18)(19), or as the cause of tumor progression (8,16,92,101).…”

mentioning

confidence: 99%

“…Moreover, several investigators have claimed diploid cancers (15,17,93,100). In view of this, aneuploidy has been interpreted either as a "Folgeerscheinung" (consequence) (15) that is not essential for carcinogensis (16)(17)(18)(19), or as the cause of tumor progression (8,16,92,101). In the words of Mitelman et al, aneuploidy is ''secondary'' because, first, ''practically every numerical change may be found-even as the sole anomaly-in almost every neoplastic disorder; second, because the pathogenetic significance of such abnormalities is totally unknown; and, third, because no chromosomal breakpoints are involved'' (5)-although a cancer-specific or consistent aneuploidy is not postulated by Boveri's hypothesis.…”

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confidence: 99%

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Aneuploidy correlated 100% with chemical transformation of Chinese hamster cells

Yerganian

Duesberg

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

162

111

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Aneuploidy or chromosome imbalance is the most massive genetic abnormality of cancer cells. It used to be considered the cause of cancer when it was discovered more than 100 years ago. Since the discovery of the gene, the aneuploidy hypothesis has lost ground to the hypothesis that mutation of cellular genes causes cancer. According to this hypothesis, cancers are diploid and aneuploidy is secondary or nonessential. Here we reexamine the aneuploidy hypothesis in view of the fact that nearly all solid cancers are aneuploid, that many carcinogens are nongenotoxic, and that mutated genes from cancer cells do not transform diploid human or animal cells. By regrouping the gene pool-as in speciation-aneuploidy inevitably will alter many genetic programs. This genetic revolution can explain the numerous unique properties of cancer cells, such as invasiveness, dedifferentiation, distinct morphology, and specific surface antigens, much better than gene mutation, which is limited by the conservation of the existing chromosome structure. To determine whether aneuploidy is a cause or a consequence of transformation, we have analyzed the chromosomes of Chinese hamster embryo (CHE) cells transformed in vitro. This system allows (i) detection of transformation within 2 months and thus about 5 months sooner than carcinogenesis and (ii) the generation of many more transformants per cost than carcinogenesis. To minimize mutation of cellular genes, we have used nongenotoxic carcinogens. It was found that 44 out of 44 colonies of CHE cells transformed by benz[a]pyrene, methylcholanthrene, dimethylbenzanthracene, and colcemid, or spontaneously were between 50 and 100% aneuploid. Thus, aneuploidy originated with transformation. Two of two chemically transformed colonies tested were tumorigenic 2 months after inoculation into hamsters. The cells of transformed colonies were heterogeneous in chromosome number, consistent with the hypothesis that aneuploidy can perpetually destabilize the chromosome number because it unbalances the elements of the mitotic apparatus. Considering that all 44 transformed colonies analyzed were aneuploid, and the early association between aneuploidy, transformation, and tumorigenicity, we conclude that aneuploidy is the cause rather than a consequence of transformation.

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Das Krebsproblem

Cited by 280 publications

References 0 publications

Is carcinogenesis a form of speciation?

Is carcinogenesis a form of speciation?

Aneuploidy and Cancer: From Correlation to Causation

Aneuploidy correlated 100% with chemical transformation of Chinese hamster cells

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