Combined Effects of Tumor Promoters and Serum on Proliferin mRNA Induction: A Biomarker Sensitive to Saccharin, 2,3,7,8-Tcdd, and Other Compounds at Minimal Concentrations Promoting C3H/10T1/2 Cell Transformation

Parfett, Craig L.J.

doi:10.1080/713853957

Cited by 10 publications

(6 citation statements)

References 45 publications

(52 reference statements)

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“…It is possible that the cocarcinogenic properties of formaldehyde and acetaldehyde derive from their toxicity and subsequent stimulation of cell proliferation, , which would increase the initiating potential of NNK. Both acetaldehyde and formaldehyde promote cell transformation in C3 H /10T1/2 cell cultures . These aldehydes also alter gene expression in ways that could enhance tumor initiation by NNK.…”

Section: Discussionmentioning

confidence: 99%

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Coexposure to Inhaled Aldehydes or Carbon Dioxide Enhances the Carcinogenic Properties of the Tobacco-Specific Nitrosamine 4-Methylnitrosamino-1-(3-pyridyl)-1-butanone in the A/J Mouse Lung

Peterson

Oram

Flavin

et al. 2021

Chem. Res. Toxicol.

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Tobacco smoke is a complex mixture of chemicals, many of which are toxic and carcinogenic. Hazard assessments of tobacco smoke exposure have predominantly focused on either single chemical exposures or the more complex mixtures of tobacco smoke or its fractions. There are fewer studies exploring interactions between specific tobacco smoke chemicals. Aldehydes such as formaldehyde and acetaldehyde were hypothesized to enhance the carcinogenic properties of the human carcinogen, 4-methylnitrosamino-1-(3-pyridyl)-1-butanone (NNK) through a variety of mechanisms. This hypothesis was tested in the established NNKinduced A/J mouse lung tumor model. A/J mice were exposed to NNK (intraperitoneal injection, 0, 2.5, or 7.5 μmol in saline) in the presence or absence of acetaldehyde (0 or 360 ppmv) or formaldehyde (0 or 17 ppmv) for 3 h in a nose-only inhalation chamber, and lung tumors were counted 16 weeks later. Neither aldehyde by itself induced lung tumors. However, mice receiving both NNK and acetaldehyde or formaldehyde had more adenomas with dysplasia or progression than those receiving only NNK, suggesting that aldehydes may increase the severity of NNK-induced lung adenomas. The aldehyde coexposure did not affect the levels of NNK-derived DNA adduct levels. Similar studies tested the ability of a 3 h nose-only carbon dioxide (0, 5, 10, or 15%) coexposure to influence lung adenoma formation by NNK. While carbon dioxide alone was not carcinogenic, it significantly increased the number of NNK-derived lung adenomas without affecting NNKderived DNA damage. These studies indicate that the chemicals in tobacco smoke work together to form a potent lung carcinogenic mixture.

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Section: Discussionmentioning

confidence: 99%

“…Both acetaldehyde and formaldehyde promote cell transformation in C3H/10T1/2 cell cultures. 56 These aldehydes also alter gene expression in ways that could enhance tumor initiation by NNK. For example, both acetaldehyde and formaldehyde reduce apoptotic activity.…”

Section: ■ Discussionmentioning

confidence: 99%

Coexposure to Inhaled Aldehydes or Carbon Dioxide Enhances the Carcinogenic Properties of the Tobacco-Specific Nitrosamine 4-Methylnitrosamino-1-(3-pyridyl)-1-butanone in the A/J Mouse Lung

Peterson

Oram

Flavin

et al. 2021

Chem. Res. Toxicol.

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“…Other genes, such as metallothionin and prostaglandin H synthase‐2, respond to TPA and several other tumor promoters, but not to BPO [43,44]. Mrp/plf ‐mRNA has been shown to increase in vitro in response to 17 different promoters of cell transformation [7] and may therefore parallel the response‐pattern of the more broadly responsive gene group. Additional studies in skin with all of these genes and a broader range of skin tumor promoters will be required to confirm this conjecture.…”

Section: Discussionmentioning

confidence: 99%

“…The 596 bp cDNA fragment contains only the upstream primer‐site targeted by the mrp/plf ‐specific PCR primer‐pair used in other parts of this study (see below), thereby minimizing chances for spurious amplifications because of cross‐contamination of laboratory ware or PCR solutions. Blot prehybridization, hybridization, washing, and probe stripping procedures were carried out as described previously [7]. Developed autoradiographic images within the linear response range of Kodak BioMax film (optical density 0.2–2.0) were quantified with a Molecular Dynamics 300B scanning/computing densitometer and Image Quant software.…”

Section: Methodsmentioning

confidence: 99%

“…In tumor promotion experiments in vivo and in vitro, where such nongenotoxic carcinogens are readily detected, many short‐term changes in cellular biochemistry and cell biological behavior are contingent upon carcinogen‐induced imbalances of oxyradical generation and degradation [5,6]. In the murine C3H/10T1/2 cell model of multi‐stage carcinogenesis, the short‐term response of the mitogen‐regulated protein/proliferin ( mrp/plf ) gene family has been shown to be a reliable predictor of promotional effects by various agents in two‐stage morphological transformation assays, including agents that are inefficient genotoxins [7,8]. Oxyradical production induces plf ‐mRNA levels while antioxidants are inhibitory [9,10], in parallel to the effects of oxidants and antioxidants on the promotion of transformation in these cells [11].…”

Section: Introductionmentioning

confidence: 99%

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Mitogen‐regulated protein/proliferin mRNA induction following single applications of tumor promoters to murine skin

Parfett

2005

Molecular Carcinogenesis

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Mitogen-regulated protein/proliferin (mrp/plf) gene family transcripts rise in abundance as a response to diverse chemical and physical agents that promote morphological transformation in the murine C3H/10T1/2 cultured cell model of multi-step carcinogenesis. To determine if proliferin genes respond to tumor promoters in vivo, RNA was extracted from the whole skin of SENCAR mice after single applications of 2 or 20 microg 12-O-tetradecanoylphorbol-13-acetate (TPA); 3.2 or 32 nmole), 20 or 40 mg benzoyl peroxide (BPO; 83, 165 micromole), or acetone vehicle alone (2.72 mmole). RNA samples were prepared from treated skin areas, 2-48 h after painting. Mrp/plf-mRNA was not detected in Northern blot hybridizations, but large increases in mRNAs for ornithine decarboxylase gene and mRNA (odc), v-jun oncogene-related transcription factor gene and mRNA (junB), egr1 (early growth response protein gene and mRNA) were measured relative to beta 2 microglobulin gene and mRNA (b2m) mRNA in response to TPA. BPO induced small relative changes in these mRNAs. Reverse transcriptase (RT)-polymerase chain reactions (PCR) detected fully-processed MRP/plf-mRNA 16-48 h after TPA treatments in five of six animals, and in three of six BPO-treated animals. The MRP/plf-mRNA species expressed in the skin were predominantly plf1 and mrp3 as determined by gene-specific restriction enzyme sites within the RT-PCR products. Expression was either undetectable or found at low levels in acetone-painted controls and was not detected during the anagen phase of the normal hair growth cycle in unpainted animals. These results demonstrate that mrp/plf-mRNA is differentially expressed in murine skin in response to mechanistically distinct tumor promoters and has potential utility as a short-term biomarker for tumor promoting effects in chemical carcinogenesis.

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Chronic Effects of Cigarette Smoke on the Respiratory Tract

Peterson,

Wattenberg

2024

Reference Module in Biomedical Sciences

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Combined Effects of Tumor Promoters and Serum on Proliferin mRNA Induction: A Biomarker Sensitive to Saccharin, 2,3,7,8-Tcdd, and Other Compounds at Minimal Concentrations Promoting C3H/10T1/2 Cell Transformation

Cited by 10 publications

References 45 publications

Coexposure to Inhaled Aldehydes or Carbon Dioxide Enhances the Carcinogenic Properties of the Tobacco-Specific Nitrosamine 4-Methylnitrosamino-1-(3-pyridyl)-1-butanone in the A/J Mouse Lung

Coexposure to Inhaled Aldehydes or Carbon Dioxide Enhances the Carcinogenic Properties of the Tobacco-Specific Nitrosamine 4-Methylnitrosamino-1-(3-pyridyl)-1-butanone in the A/J Mouse Lung

Mitogen‐regulated protein/proliferin mRNA induction following single applications of tumor promoters to murine skin

Chronic Effects of Cigarette Smoke on the Respiratory Tract

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