The Chemical Production of Mutations

Auerbach, C.; Robson, J. M.; Carr, J. G.

doi:10.1126/science.105.2723.243

Cited by 318 publications

(34 citation statements)

References 13 publications

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“…The types of mutants produced are somewhat different from those produced by high-energy radiation, and of a type which agrees with the suggestion that less energy is involved in the mutation (e.g. mosaic production) (Auerbach, Robson and Carr, 1947). The hydrocarbons are possibly even less energetic, and thus may only be able to produce mutations in genes that are of less stability than most.…”

Section: Methodsupporting

confidence: 71%

“…In this connection the negative result on Drosophila melanogaster with carcinogenic hydrocarbons is perhaps significant. Furthermore, compounds such as acetylaminofluorene and urethane produce cancer, but have not yet been shown to produce mutations, while mustard gas and analogues will produce mutations, but have not yet been demonstrated to have any carcinogenic action (Auerbach, Robson and Carr, 1947), though they possess an anti-carcinogenic effect. Clearly, much work remains to be done before these results can be safely used as a basis for generalizations.…”

Section: Methodmentioning

confidence: 99%

“…This substance had previously been tested on Drosophila melanogaster (Auerbach, 1939), and found not to produce lethal mutations in this species. In an experiment in which 1:2:5:6-dibenzanthracene was being given to mice, and the offspring used for breeding, it was regarded as possible that mutations might appear, though because of the nature and size of the experiment it was felt that the chance of any being detected was so small as to be negligible.…”

mentioning

confidence: 99%

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Production of Mutations in Mice by 1:2:5:6-Dibenzanthracene

Jg¹

1947

Br J Cancer

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Section: Methodsupporting

confidence: 71%

Section: Methodmentioning

confidence: 99%

mentioning

confidence: 99%

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Production of Mutations in Mice by 1:2:5:6-Dibenzanthracene

Jg¹

1947

Br J Cancer

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“…(ii) Soon after the discovery of genes, some classical carcinogens were shown to be mutagenic, such as x-rays in 1927 (22) and alkylating agents in the 1940s (23). As more and more carcinogens were found to be mutagenic with ever more sensitive mutagenicity tests (17,(24)(25)(26)(27)102), the gene mutation hypothesis reached a high point in 1973 with the premise that "carcinogens are mutagens" (28).…”

mentioning

confidence: 99%

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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“…During and directly following the Second World War, radiation-based techniques were complemented by chemical mutagens that were less destructive, freely available, and easier to work with. Pioneer work in this area was performed by Auerbach and others, who demonstrated an increased mutation frequency in Drosophila following exposure to mustard gas (War Gas) [13, 14]. A few years later, this work was followed by the discovery of methane-sulphonates and other chemical mutagens, which are still in use today [15].…”

Section: Mutagenesis and Tillingmentioning

confidence: 99%

Mutagenesis as a Tool in Plant Genetics, Functional Genomics, and Breeding

Sikora

Chawade

Larsson

et al. 2011

International Journal of Plant Genomics

203

137

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Plant mutagenesis is rapidly coming of age in the aftermath of recent developments in high-resolution molecular and biochemical techniques. By combining the high variation of mutagenised populations with novel screening methods, traits that are almost impossible to identify by conventional breeding are now being developed and characterised at the molecular level. This paper provides a comprehensive overview of the various techniques and workflows available to researchers today in the field of molecular breeding, and how these tools complement the ones already used in traditional breeding. Both genetic (Targeting Induced Local Lesions in Genomes; TILLING) and phenotypic screens are evaluated. Finally, different ways of bridging the gap between genotype and phenotype are discussed.

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The Chemical Production of Mutations

Cited by 318 publications

References 13 publications

Production of Mutations in Mice by 1:2:5:6-Dibenzanthracene

Production of Mutations in Mice by 1:2:5:6-Dibenzanthracene

Aneuploidy correlated 100% with chemical transformation of Chinese hamster cells

Mutagenesis as a Tool in Plant Genetics, Functional Genomics, and Breeding

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