The genetic toxicology of 5-bromodeoxyuridine in mammalian cells

Morris, Suzanne M.

doi:10.1016/0165-1110(91)90007-i

Cited by 111 publications

(72 citation statements)

References 276 publications

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“…BrdUrd is incorporated into replicating DNA in place of thymidine, and this effect is mutagenic [170]. In addition to the usual keto form, BrdUrd may assume an enol tautomeric form, which forms hydrogen bonds with guanine instead of adenine, the normal pair for thymidine and 5-bromouracil.…”

Section: Do Carcinogens Accelerate Aging?mentioning

confidence: 99%

“…In addition to the usual keto form, BrdUrd may assume an enol tautomeric form, which forms hydrogen bonds with guanine instead of adenine, the normal pair for thymidine and 5-bromouracil. In the absence of 5-bromouracil repair in rat DNA [171], if BrdUrd is incorporated into DNA as the enol tautomer, base pair substitution mutations are expected to occur (GC 0/AT and AT 0/ GC transitions) during subsequent DNA replication [170]. Unlike purine-analogues, BrdUrd is not involved in energy production or in cell-signaling and interactions and hence can reach required levels of mutations, while being less toxic than in the case of 'spoiled' analogues of purines [172].…”

Section: Do Carcinogens Accelerate Aging?mentioning

confidence: 99%

“…Unlike purine-analogues, BrdUrd is not involved in energy production or in cell-signaling and interactions and hence can reach required levels of mutations, while being less toxic than in the case of 'spoiled' analogues of purines [172]. This ability to induce uniformly distributed point mutations with a chosen intensity using BrdUrd is based on the fact that the number of mutations is linearly dependent on the concentration of BrdUrd [170,173,174]. Craddock [175] observed a dose-dependent shortening in life-span of rats exposed to BrdUrd in early life, in uncontrolled experiments, without data on tumor incidence or on biomarkers of aging.…”

Section: Do Carcinogens Accelerate Aging?mentioning

confidence: 99%

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The relationship between aging and carcinogenesis: a critical appraisal

Anisimov

2003

Critical Reviews in Oncology/Hematology

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The incidence of cancer increases with age in humans and in laboratory animals alike. There are different patterns of age-related distribution of tumors in different organs and tissues. Aging may increase or decrease the susceptibility of various tissues to initiation of carcinogenesis and usually facilitates promotion and progression of carcinogenesis. Aging may predispose to cancer by several mechanisms: (1) tissue accumulation of cells in late stages of carcinogenesis; (2) alterations in homeostasis, in particular, alterations in immune and endocrine system and (3) telomere instability linking aging and increased cancer risk. Increased susceptibility to the effects of tumor promoters is found both in aged animals and aged humans, as predicted by the multistage model of carcinogenesis. Available evidence supporting the relevance of replicative senescence of human cells and telomere biology to human cancer seems quite strong, however, the evidence linking cellular senescence to human aging is controversial and required additional stuidies. Data on the acceleration of aging by carcinogenic agents as well as on increased cancer risk in patients with

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Section: Do Carcinogens Accelerate Aging?mentioning

confidence: 99%

Section: Do Carcinogens Accelerate Aging?mentioning

confidence: 99%

Section: Do Carcinogens Accelerate Aging?mentioning

confidence: 99%

See 1 more Smart Citation

The relationship between aging and carcinogenesis: a critical appraisal

Anisimov

2003

Critical Reviews in Oncology/Hematology

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“…1). However, BrdU is also considered to be a mutagen (Morris, 1991), and thus the higher doses may complicate the results in unpredictable ways. Significantly, many factors and external agents that modulate the proliferation of granule cells, such as seizures, are also known to cause cell damage leading to their death (Bengzon et al, 1997).…”

Section: Are All Brdu-labeled Cells New?mentioning

confidence: 99%

Adult Neurogenesis in Mammals: An Identity Crisis

2002

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“…In fact, BrdU is not physiologically neutral: rather, it is cytotoxic (reviewed by Morris, 1991). In some cases, BrdU has a dramatic influence on specific aspects of development.…”

mentioning

confidence: 99%

Dose-, time-, and tissue-dependent effects of 5-bromo-2′ -deoxyuridine on the in-vitro organogenesis of Arabidopsis thaliana

Sugiyama

Imamura

2006

Plant Cell Tiss Organ Cult

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Vigorous organogenesis can be induced from hypocotyl and root explants of Arabidopsis thaliana using a two-step culture procedure consisting of preculture on callusinducing medium (CIM) and subsequent culture on shoot-inducing medium (SIM) or root-inducing medium (RIM). With this culture system, we examined the influence of 5-bromo-2¢-deoxyuridine (BrdU), a thymidine (dT) analogue, on plant organogenesis in vitro. Treatment with BrdU during SIM or RIM culture had negative effects on shoot and root redifferentiation over a broad range of concentrations. When explants were exposed to low concentrations of BrdU during preculture and then transferred onto BrdU-free SIM, shoot redifferentiation was accelerated significantly. At higher doses, BrdU treatment during the pre-culture inhibited shoot redifferentiation strongly in hypocotyl explants, but not in root explants. This suggests that a target of the BrdU action lies within the process of acquisition of cell proliferation competence specifically involved in hypocotyl dedifferentiation. These effects of BrdU were counteracted by the simultaneous addition of excess dT. BrdUpretreated and untreated explants did not differ significantly in the phytohormone dependency of shoot redifferentiation. Our results provide a basis for future studies on plant organogenesis combining pharmacological analysis with BrdU as a probe and molecular genetics with Arabidopsis mutants.

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The genetic toxicology of 5-bromodeoxyuridine in mammalian cells

Cited by 111 publications

References 276 publications

The relationship between aging and carcinogenesis: a critical appraisal

The relationship between aging and carcinogenesis: a critical appraisal

Adult Neurogenesis in Mammals: An Identity Crisis

Dose-, time-, and tissue-dependent effects of 5-bromo-2′ -deoxyuridine on the in-vitro organogenesis of Arabidopsis thaliana

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