scholarly journals Chemical carcinogens transform BHK cells by inducing a recessive mutation.

1982 ◽  
Vol 2 (2) ◽  
pp. 97-105 ◽  
Author(s):  
N Bouck ◽  
G di Mayorca
Keyword(s):  
Neoplastic Transformation ◽  
Single Step ◽  
Recessive Mutation ◽  
Recessive Trait ◽  
Dominant Trait ◽  
Chemical Carcinogens ◽  
Bhk Cells ◽  
Chemically Induced ◽  
Resistant Mutants ◽  
Isogenic Strains

Treatment of BHK cells with mutagenic carcinogens induced neoplastic transformation in a single step. This transformation displayed the characteristics expected for a recessive mutation. Increasing doses of carcinogens induced transformants with kinetics similar to the kinetics with which they induced 6-thioguanine-resistant or ouabain-resistant mutants in the same population of cells. Transformants with temperature-restricted phenotypes were easily induced by carcinogens which cause mutations by base changes, but when ICR frameshift mutagens were used, the proportion of temperature-limited transformants was inversely related to the frequency with which a particular mutagen induced frameshift mutations. In hybrids between pseudodiploid isogenic strains of normal and transformed BHK cells, transformation was expressed as a dominant trait when the transformed parent was induced by a papovavirus, but was suppressed as a recessive trait when the transformed parent arose spontaneously or was chemically induced. Segregation of transformation was observed upon growth of suppressed normal hybrids, and the transformed phenotype which was reexpressed was in most cases characteristics of the original transformed parent.

Chemical carcinogens transform BHK cells by inducing a recessive mutation

1982 ◽  
Vol 2 (2) ◽  
pp. 97-105
Author(s):  
N Bouck ◽  
G di Mayorca
Keyword(s):  
Neoplastic Transformation ◽  
Single Step ◽  
Recessive Mutation ◽  
Recessive Trait ◽  
Dominant Trait ◽  
Chemical Carcinogens ◽  
Bhk Cells ◽  
Chemically Induced ◽  
Resistant Mutants ◽  
Isogenic Strains

Treatment of BHK cells with mutagenic carcinogens induced neoplastic transformation in a single step. This transformation displayed the characteristics expected for a recessive mutation. Increasing doses of carcinogens induced transformants with kinetics similar to the kinetics with which they induced 6-thioguanine-resistant or ouabain-resistant mutants in the same population of cells. Transformants with temperature-restricted phenotypes were easily induced by carcinogens which cause mutations by base changes, but when ICR frameshift mutagens were used, the proportion of temperature-limited transformants was inversely related to the frequency with which a particular mutagen induced frameshift mutations. In hybrids between pseudodiploid isogenic strains of normal and transformed BHK cells, transformation was expressed as a dominant trait when the transformed parent was induced by a papovavirus, but was suppressed as a recessive trait when the transformed parent arose spontaneously or was chemically induced. Segregation of transformation was observed upon growth of suppressed normal hybrids, and the transformed phenotype which was reexpressed was in most cases characteristics of the original transformed parent.

Inheritance of evolved thiocarbamate resistance in Rigid Ryegrass (Lolium rigidum) populations from Australia

Weed Science ◽  
2021 ◽  
pp. 1-19
Author(s):  
David J. Brunton ◽  
Peter Boutsalis ◽  
Gurjeet Gill ◽  
Christopher Preston
Keyword(s):  
Recessive Allele ◽  
Recessive Trait ◽  
Dominant Allele ◽  
Lolium Rigidum ◽  
Dominant Trait ◽  
Susceptible Parent ◽  
Rigid Ryegrass

Abstract Populations of rigid ryegrass (Lolium rigidum Gaudin) from southern Australia have evolved resistance to the thiocarbamate herbicide prosulfocarb. The inheritance of prosulfocarb resistance was explored by crossing R and S individuals. In all families within each cross, except 16.2, the response of the F1 were intermediate between the parents, suggesting that resistance is inherited as a single, partially dominant trait. For 16.2, the response of the F1 was more similar to the susceptible parent, suggesting resistance may be a recessive trait in this population. Segregation at the discriminating dose of 1200 g a.i. ha−1 prosulfocarb in populations 375-14 fitted the ratio (15:1) consistent with two independent dominant alleles; 198-15 fitted a ratio (13:3) for two independent alleles, one dominant and one recessive; and EP162 fitted a ratio (9:7) for two additive dominant alleles. In contrast segregation of population 16.2 fitted a (7:9) ratio consistent with two independent recessive alleles contributing to prosulfocarb resistance. Four different patterns of resistance to prosulfocarb were identified in different resistant populations, with inheritance as a dominant allele, dominant and recessive, additive dominant and as an independent recessive allele. This suggests there are several different mechanisms of prosulfocarb resistance present in L. rigidum.

Diverse carotenoids protect against chemically induced neoplastic transformation

1991 ◽  
Vol 12 (4) ◽  
pp. 671-678 ◽  
Author(s):  
John S. Bertram ◽  
Ao Pung ◽  
Melissa Churley ◽  
T. Joseph Kappock ◽  
Lynne R. Wilkins ◽  
...  
Keyword(s):  
Neoplastic Transformation ◽  
Chemically Induced

scholarly journals Antipneumococcal Activities of Two Novel Macrolides, GW 773546 and GW 708408, Compared with Those of Erythromycin, Azithromycin, Clarithromycin, Clindamycin, and Telithromycin

2004 ◽  
Vol 48 (11) ◽  
pp. 4103-4112 ◽  
Author(s):  
Vlatka Matic ◽  
Klaudia Kosowska ◽  
Bulent Bozdogan ◽  
Linda M. Kelly ◽  
Kathy Smith ◽  
...  
Keyword(s):  
Ribosomal Protein ◽  
Protein Sequence ◽  
Single Step ◽  
23S Rrna ◽  
Susceptible Parent ◽  
Rrna Sequence ◽  
Resistant Strains ◽  
Resistant Mutants ◽  
Rrna Sequences ◽  
Selection Of

ABSTRACT The MICs of GW 773546, GW 708408, and telithromycin for 164 macrolide-susceptible and 161 macrolide-resistant pneumococci were low. The MICs of GW 773546, GW 708408, and telithromycin for macrolide-resistant strains were similar, irrespective of the resistance genotypes of the strains. Clindamycin was active against all macrolide-resistant strains except those with erm(B) and one strain with a 23S rRNA mutation. GW 773546, GW 708408, and telithromycin at two times their MICs were bactericidal after 24 h for 7 to 8 of 12 strains. Serial passages of 12 strains in the presence of sub-MICs yielded 54 mutants, 29 of which had changes in the L4 or L22 protein or the 23S rRNA sequence. Among the macrolide-susceptible strains, resistant mutants developed most rapidly after passage in the presence of clindamycin, GW 773546, erythromycin, azithromycin, and clarithromycin and slowest after passage in the presence of GW 708408 and telithromycin. Selection of strains for which MICs were ≥0.5 μg/ml from susceptible parents occurred only with erythromycin, azithromycin, clarithromycin, and clindamycin; 36 resistant clones from susceptible parent strains had changes in the sequences of the L4 or L22 protein or 23S rRNA. No mef(E) strains yielded resistant clones after passage in the presence of erythromycin and azithromycin. Selection with GW 773546, GW 708408, telithromycin, and clindamycin in two mef(E) strains did not raise the erythromycin, azithromycin, and clarithromycin MICs more than twofold. There were no change in the ribosomal protein (L4 or L22) or 23S rRNA sequences for 15 of 18 mutants selected for macrolide resistance; 3 mutants had changes in the L22-protein sequence. GW 773546, GW 708408, and telithromycin selected clones for which MICs were 0.03 to >2.0 μg/ml. Single-step studies showed mutation frequencies <5.0 × 10−10 to 3.5 × 10−7 for GW 773546, GW 708408, and telithromycin for macrolide-susceptible strains and 1.1 × 10−7 to >4.3 × 10−3 for resistant strains. The postantibiotic effects of GW 773546, GW 708408, and telithromycin were 2.4 to 9.8 h.

scholarly journals Dual Targeting of DNA Gyrase and Topoisomerase IV: Target Interactions of Garenoxacin (BMS-284756, T-3811ME), a New Desfluoroquinolone

2002 ◽  
Vol 46 (11) ◽  
pp. 3370-3380 ◽  
Author(s):  
Dilek Ince ◽  
Xiamei Zhang ◽  
L. Christine Silver ◽  
David C. Hooper
Keyword(s):  
Inhibitory Concentration ◽  
Efflux Pump ◽  
Fold Increase ◽  
Single Step ◽  
The Novel ◽  
Wild Type ◽  
Topoisomerase Iv ◽  
Dual Targeting ◽  
Resistant Mutants ◽  
Selection Of

ABSTRACT We determined the target enzyme interactions of garenoxacin (BMS-284756, T-3811ME), a novel desfluoroquinolone, in Staphylococcus aureus by genetic and biochemical studies. We found garenoxacin to be four- to eightfold more active than ciprofloxacin against wild-type S. aureus. A single topoisomerase IV or gyrase mutation caused only a 2- to 4-fold increase in the MIC of garenoxacin, whereas a combination of mutations in both loci caused a substantial increase (128-fold). Overexpression of the NorA efflux pump had minimal effect on resistance to garenoxacin. With garenoxacin at twice the MIC, selection of resistant mutants (<7.4 × 10−12 to 4.0 × 10−11) was 5 to 6 log units less than that with ciprofloxacin. Mutations inside or outside the quinolone resistance-determining regions (QRDR) of either topoisomerase IV, or gyrase, or both were selected in single-step mutants, suggesting dual targeting of topoisomerase IV and gyrase. Three of the novel mutations were shown by genetic experiments to be responsible for resistance. Studies with purified topoisomerase IV and gyrase from S. aureus also showed that garenoxacin had similar activity against topoisomerase IV and gyrase (50% inhibitory concentration, 1.25 to 2.5 and 1.25 μg/ml, respectively), and although its activity against topoisomerase IV was 2-fold greater than that of ciprofloxacin, its activity against gyrase was 10-fold greater. This study provides the first genetic and biochemical data supporting the dual targeting of topoisomerase IV and gyrase in S. aureus by a quinolone as well as providing genetic proof for the expansion of the QRDRs to include the 5′ terminus of grlB and the 3′ terminus of gyrA.

scholarly journals Speciation Theory of Carcinogenesis Explains Karyotypic Individuality and Long Latencies of Cancers

Genes ◽  
2018 ◽  
Vol 9 (8) ◽  
pp. 402 ◽  
Author(s):  
Ankit Hirpara ◽  
Mathew Bloomfield ◽  
Peter Duesberg
Keyword(s):  
Chromosomal Instability ◽  
Normal Cell ◽  
Neoplastic Transformation ◽  
Single Step ◽  
Chain Reactions ◽  
Mutation Theory ◽  
Normal Human ◽  
Low Probability ◽  
Carcinogen Exposure ◽  
The Individual

It has been known for over 100 years that cancers have individual karyotypes and arise only years to decades after initiating carcinogens. However, there is still no coherent theory to explain these definitive characteristics of cancer. The prevailing mutation theory holds that cancers are late because the primary cell must accumulate 3–8 causative mutations to become carcinogenic and that mutations, which induce chromosomal instability (CIN), generate the individual karyotypes of cancers. However, since there is still no proven set of mutations that transforms a normal to a cancer cell, we have recently advanced the theory that carcinogenesis is a form of speciation. This theory predicts carcinogens initiate cancer by inducing aneuploidy, which automatically unbalances thousands of genes and thus catalyzes chain-reactions of progressive aneuploidizations. Over time, these aneuploidizations have two endpoints, either non-viable karyotypes or very rarely karyotypes of new autonomous and immortal cancers. Cancer karyotypes are immortalized despite destabilizing congenital aneuploidy by clonal selections for autonomy—similar to those of conventional species. This theory predicts that the very low probability of converting the karyotype of a normal cell to that of a new autonomous cancer species by random aneuploidizations is the reason for the karyotypic individuality of new cancers and for the long latencies from carcinogens to cancers. In testing this theory, we observed: (1) Addition of mutagenic and non-mutagenic carcinogens to normal human and rat cells generated progressive aneuploidizations months before neoplastic transformation. (2) Sub-cloning of a neoplastic rat clone revealed heritable individual karyotypes, rather than the non-heritable karyotypes predicted by the CIN theory. (3) Analyses of neoplastic and preneoplastic karyotypes unexpectedly identified karyotypes with sets of 3–11 new marker chromosomes without detectable intermediates, consistent with single-step origins. We conclude that the speciation theory explains logically the long latencies from carcinogen exposure and the individuality of cancers. In addition, the theory supports the single-step origins of cancers, because karyotypic autonomy is all-or-nothing. Accordingly, we propose that preneoplastic aneuploidy and clonal neoplastic karyotypes provide more reliable therapeutic indications than current analyses of thousands of mutations.

scholarly journals Features of the inheritance of fruit size in the hybrid families of prunus domestica

2020 ◽  
Vol 17 ◽  
pp. 00070
Author(s):  
G. E. Osipov ◽  
Z. A. Osipova
Keyword(s):  
Fruit Size ◽  
Recessive Trait ◽  
Fruit Crops ◽  
Prunus Domestica ◽  
Dominant Trait ◽  
Small Fruit ◽  
Russian Research Institute ◽  
Selection Of ◽  
Russian Research ◽  
Research Institute

The aim of the research was to establish the features of the inheritance of the size of the fruit in the hybrid families of Prunus domestica. The objects of study were hybrid seedlings of plum selection of the Tatar research Institute of agriculture. Fruit sizes were estimated according to the methodology of the all-Russian research Institute of fruit crops selection. The analysis of the splitting of plum in hybrid families by the size of fruits showed that seedlings with small fruits dominated in the breeding gardens of the Tatar research Institute. The size of the plum fruit is controlled by polygens. All of the original parental forms are heterozygotes for the genes determining the size of the fruit. A small fruit is a dominant trait, a large fruit is a recessive trait. In most hybrid families, plum seedlings have a significant variability in the size of the fruit. Transgressive genotypes with large fruits are formed in hybrid families Eurasia 21 x Renklod Tenkovsky, Eurasia 21 x free pollination and Zyuzinskaya x free pollination. The varieties Eurasia 21 and Zyuzinskaya must be used as sources in breeding of plums for large-fruited.

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