title: Mitotic crossover--an evolutionary rudiment which promotes carcinogenesis of colorectal carcinoma.
abstract: Mitotic crossover is a natural mechanism that is a main source of the genetic variability of primitive organisms. In complex organisms such as mammals, it represents an evolutionary rudiment which persisted as one of the numerous DNA repair mechanisms, and results in the production of homozygous allele combinations in all heterozygous genes located on the chromosome arm distal to the crossover. This event is familiar as loss of heterozygosity, which is one of the key mechanisms responsible for the development and progression of almost all cancers. We propose the hypothesis in which mitotic crossover is a principal source of the increased loss of heterozygosity that leads to the initiation and progression of colorectal carcinoma. The hypothesis could be tested by in vitro inhibition of Rad51 protein, orthotopic grafting of human colon cancer tissue into the gut of mice, and treatment with potential inhibitors. After these procedures, the frequency of mitotic crossover would be estimated. The development of selective inhibitors of mitotic crossover could stop further carcinogenesis of colorectal carcinoma, as well as many other neoplastic events. Loss of heterozygosity is an event responsible for carcinogenesis, its reduction by selective inhibitors of mitotic crossover could have a positive effect on cancer chemoprevention, as well as on growth reduction and a cessation in the progression of earlier developed tumors.
authors.affiliation: Branislav Rovcanin, Institute for Human Genetics, Faculty of Medicine, University of Belgrade, Belgrade 11000, Serbia.
authors.forename: Branislav
authors.initials: B
authors.lastname: Rovcanin
authors.affiliation: Branislav Rovcanin, Institute for Human Genetics, Faculty of Medicine, University of Belgrade, Belgrade 11000, Serbia.
authors.forename: Ivan
authors.initials: I
authors.lastname: Ivanovski
authors.affiliation: Branislav Rovcanin, Institute for Human Genetics, Faculty of Medicine, University of Belgrade, Belgrade 11000, Serbia.
authors.forename: Olivera
authors.initials: O
authors.lastname: Djuric
authors.affiliation: Branislav Rovcanin, Institute for Human Genetics, Faculty of Medicine, University of Belgrade, Belgrade 11000, Serbia.
authors.forename: Dimitrije
authors.initials: D
authors.lastname: Nikolic
authors.affiliation: Branislav Rovcanin, Institute for Human Genetics, Faculty of Medicine, University of Belgrade, Belgrade 11000, Serbia.
authors.forename: Jelena
authors.initials: J
authors.lastname: Petrovic
authors.affiliation: Branislav Rovcanin, Institute for Human Genetics, Faculty of Medicine, University of Belgrade, Belgrade 11000, Serbia.
authors.forename: Petar
authors.initials: P
authors.lastname: Ivanovski
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002277:Carcinoma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019143:Evolution, Molecular; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D014644:Genetic Variation; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D019656:Loss of Heterozygosity; D008938:Mitosis / Q000187:drug effects / Q000235:genetics*; D058990:Molecular Targeted Therapy; D011995:Recombination, Genetic / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents
keywords: Cancer chemoprevention; Carcinogenesis; Colorectal carcinoma; Inhibitors; Loss of heterozygosity; Mitotic crossing over