Growth inhibition and DNA damage induced by benzo[a]pyrene and formaldehyde in primary cultures of rat tracheal epithelial cells

Cosma, Greg; Jamasbi, Roubadeh; Marchok, Ann C.

doi:10.1016/0027-5107(88)90122-4

Cited by 41 publications

(16 citation statements)

References 13 publications

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“…Interestingly, FA is a very potent DPC-inducer in vitro , but is a poor DPC-inducer in vivo , indicating that FA is efficiently detoxified by metabolic enzymes and chemical reactions with cellular constituents such as glutathione (54). In the present study we systematically analyzed the in vitro and in vivo half-lives of aldehyde-induced DPCs, since they have not previously been systematically assessed in a unified way (41–43,55,56). Although rigorous analysis of in vivo DPC stability was not possible due to considerable data scatter and the delayed formation of DPCs, precise analyses of in vitro half-lives revealed the induction of unstable and stable DPCs with half-lives of 2.4–6.8 h and 23.9–103.5 h, respectively (Table 2).…”

Section: Discussionmentioning

confidence: 99%

Detection of DNA–protein crosslinks (DPCs) by novel direct fluorescence labeling methods: distinct stabilities of aldehyde and radiation-induced DPCs

Shoulkamy

Nakano

Ohshima

et al. 2012

Nucleic Acids Research

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Proteins are covalently trapped on DNA to form DNA–protein crosslinks (DPCs) when cells are exposed to DNA-damaging agents. DPCs interfere with many aspects of DNA transactions. The current DPC detection methods indirectly measure crosslinked proteins (CLPs) through DNA tethered to proteins. However, a major drawback of such methods is the non-linear relationship between the amounts of DNA and CLPs, which makes quantitative data interpretation difficult. Here we developed novel methods of DPC detection based on direct CLP measurement, whereby CLPs in DNA isolated from cells are labeled with fluorescein isothiocyanate (FITC) and quantified by fluorometry or western blotting using anti-FITC antibodies. Both formats successfully monitored the induction and elimination of DPCs in cultured cells exposed to aldehydes and mouse tumors exposed to ionizing radiation (carbon-ion beams). The fluorometric and western blotting formats require 30 and 0.3 μg of DNA, respectively. Analyses of the isolated genomic DPCs revealed that both aldehydes and ionizing radiation produce two types of DPC with distinct stabilities. The stable components of aldehyde-induced DPCs have half-lives of up to days. Interestingly, that of radiation-induced DPCs has an infinite half-life, suggesting that the stable DPC component exerts a profound effect on DNA transactions over many cell cycles.

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Section: Discussionmentioning

confidence: 99%

Detection of DNA–protein crosslinks (DPCs) by novel direct fluorescence labeling methods: distinct stabilities of aldehyde and radiation-induced DPCs

Shoulkamy

Nakano

Ohshima

et al. 2012

Nucleic Acids Research

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“…DNA–protein cross-links are thought to be important genotoxic lesions induced by environmental agents and carcinogens, such as ultraviolet light (Smith 1962), formaldehyde (Cosma et al 1988), and cis - or trans -platinum (II) diammine dichlorides (Banjar et al 1984). Unlike strand breaks and other DNA lesions that are readily repaired, DPCs are relatively persistent in the cells (Lei et al1995; Oleinick et al1987).…”

Section: Discussionmentioning

confidence: 99%

Unventilated Indoor Coal-Fired Stoves in Guizhou Province, China: Cellular and Genetic Damage in Villagers Exposed to Arsenic in Food and Air

Zhang

Hong

Yang

et al. 2007

Environ Health Perspect

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BackgroundInorganic arsenic (iAs) is a well-known human carcinogen recognized by the World Health Organization and the International Agency for Research on Cancer. Currently, most iAs studies in populations are concerned with drinking water and occupational arsenicosis. In Guizhou province, arsenicosis caused by the burning of coal in unventilated indoor stoves is an unusual type of exposure. Because the poisoning mechanism involved in arsenicosis is as yet unknown and no effective therapy exists, progress has been slow on the prevention and therapy of arsenicosis.ObjectivesWe examined the relationship between arsenic (As) exposure from the burning of coal in unventilated indoor stoves and genetic damage in humans, using cellular and molecular indices. We selected villagers from Jiaole township, Guizhou province, China, who had been exposed to milligram levels of As daily via food and air contaminated by the burning of As-containing coal in unventilated indoor stoves.ResultsThe As-exposed subjects from Jiaole were divided into four groups according to skin lesion symptoms: nonpatients, mild, intermediate, and severe arsenicosis. Another 53 villagers from a town 12 km from Jiaole were recruited as the external control group. In the four groups of exposed subjects, As concentrations in urine and hair were 76–145 μg/L and 5.4–7.9 μg/g, respectively. These values were higher than those in the external control group, which had As concentrations of 46 μg/L for urine and 1.6 μg/g for hair. We measured sister chromatid exchange and chromosomal aberrations to determine human chromosome damage, and for DNA damage, we measured DNA single-strand breaks and DNA–protein cross-links. All measurements were higher in the four exposed groups compared with the external control group. DNA repair was impaired by As exposure, as indicated by the mRNA of O-6-methylguanine-DNA methyltransferase (MGMT), X-ray repair complementing defective repair in Chinese hamster cells 1 (XRCC1), and, to a lesser extent, by the mismatch repair gene hMSH2 mRNA. The expression of mutant-type p53 increased with aggravation of arsenicosis symptoms, whereas the expression of p16-INK4(p16) decreased. p53 mutated at a frequency of 30–17% in the carcinoma (n = 10) and precarcinoma (n = 12) groups. No mutation was found in p16, although deletion was evident. Deletion rates were 8.7% (n = 23) and 38.9% (n = 18) in noncarcinoma and carcinoma groups, respectively.ConclusionsThe results showed that long-term As exposure may be associated with damage of chromosomes and DNA, gene mutations, gene deletions, and alterations of DNA synthesis and repair ability.

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“…The minimum concentration at which these effects occur in vitro is about 0.05 mM (Cosma et al, 1988;Craft et al, 1987;Merk and Speit, 1998;Ross and Shipley, 1980;Speit and Merk, 2002), which suggests that the responses are observed only when the exogenous concentration approaches or exceeds the normal endogenous value. The endogenous concentration is maintained by a variety of metabolic pathways as discussed above, which together would exert a kind of ''buffering'' effect in vivo.…”

Section: Implications For the Possibility Of Leukemia Inductionmentioning

confidence: 95%

The implausibility of leukemia induction by formaldehyde: a critical review of the biological evidence on distant-site toxicity

Heck¹,

Casanova²

2004

Regulatory Toxicology and Pharmacology

182

131

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Growth inhibition and DNA damage induced by benzo[a]pyrene and formaldehyde in primary cultures of rat tracheal epithelial cells

Cited by 41 publications

References 13 publications

Detection of DNA–protein crosslinks (DPCs) by novel direct fluorescence labeling methods: distinct stabilities of aldehyde and radiation-induced DPCs

Detection of DNA–protein crosslinks (DPCs) by novel direct fluorescence labeling methods: distinct stabilities of aldehyde and radiation-induced DPCs

Unventilated Indoor Coal-Fired Stoves in Guizhou Province, China: Cellular and Genetic Damage in Villagers Exposed to Arsenic in Food and Air

The implausibility of leukemia induction by formaldehyde: a critical review of the biological evidence on distant-site toxicity

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