Skin tumorigenic potential of aflatoxin B1 in mice

Rastogi, Shipra; Dogra, R.K.S.; Khanna, Subhash K.; Das, Mukul

doi:10.1016/j.fct.2005.09.008

Cited by 39 publications

(17 citation statements)

References 29 publications

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“…This is an important aspect from the point of view of developing countries in tropics including India where manual labour is employed without any protective measure during pre- and post-harvest stages of agriculture, thereby causing a probable exposure risk through dermal route. In this regard our prior studies have revealed that dermal exposure to some mycotoxins viz aflatoxin B1 (AFB1), patulin and citrinin caused skin toxicity including tumor formation [11]–[14]. However, no such data is available for OTA.…”

Section: Introductionmentioning

confidence: 99%

Topical Application of Ochratoxin A Causes DNA Damage and Tumor Initiation in Mouse Skin

et al. 2012

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Skin cancer is one of the most common forms of cancer and 2–3 million new cases are being diagnosed globally each year. Along with UV rays, environmental pollutants/chemicals including mycotoxins, contaminants of various foods and feed stuffs, could be one of the aetiological factors of skin cancer. In the present study, we evaluated the DNA damaging potential and dermal carcinogenicity of a mycotoxin, ochratoxin A (OTA), with the rationale that dermal exposure to OTA in workers may occur during their involvement in pre and post harvest stages of agriculture. A single topical application of OTA (20–80 µg/mouse) resulted in significant DNA damage along with elevated γ-H2AX level in skin. Alteration in oxidative stress markers such as lipid peroxidation, protein carbonyl, glutathione content and antioxidant enzymes was observed in a dose (20–80 µg/mouse) and time-dependent (12–72 h) manner. The oxidative stress was further emphasized by the suppression of Nrf2 translocation to nucleus following a single topical application of OTA (80 µg/mouse) after 24 h. OTA (80 µg/mouse) application for 12–72 h caused significant enhancement in- (a) reactive oxygen species generation, (b) activation of ERK1/2, p38 and JNK MAPKs, (c) cell cycle arrest at G0/G1 phase (37–67%), (d) induction of apoptosis (2.0–11.0 fold), (e) expression of p53, p21/waf1, (f) Bax/Bcl-2 ratio, (g) cytochrome c level, (h) activities of caspase 9 (1.2–1.8 fold) and 3 (1.7–2.2 fold) as well as poly ADP ribose polymerase cleavage. In a two-stage mouse skin tumorigenesis protocol, it was observed that a single topical application of OTA (80 µg/mouse) followed by twice weekly application of 12-O-tetradecanoylphorbol-13-acetate for 24 week leads to tumor formation. These results suggest that OTA has skin tumor initiating property which may be related to oxidative stress, MAPKs signaling and DNA damage.

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Section: Introductionmentioning

confidence: 99%

Topical Application of Ochratoxin A Causes DNA Damage and Tumor Initiation in Mouse Skin

et al. 2012

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“…Rastogi et al were the first to study the skin tumorigenic potential of AFB1 using a two-stage mouse skin tumor protocol 15 . In their study, skin topical application of AFB1 (80 nmol) as a tumor initiator, followed by twice weekly application of TPA (4 nmol) for up to 24 weeks, resulted in tumor formation (squamous cell carcinoma) after 13 weeks, but no skin tumorigenic potential was observed when AFB1 was used either as a complete carcinogen (16 nmol) or as a tumor promoter (4 nmol) 15 .…”

Section: Mycotoxin-induced Dermal Toxicity Andtumorigenesismentioning

confidence: 99%

“…This is important because the skin is the major interface between the body and surrounding environment, and there is a chance that the skin of grain handling workers as well as of domestic animals is exposed to mycotoxins 10 , 11 , 12 . Concerning this point, it has been shown that such mycotoxins as aflatoxin B1 (AFB1) 13 , 14 , 15 and T-2 toxin 14 , 16 , 17 readily penetrate through human and animal skin and cause systemic toxic effects in their respective organs and also in the brain 18 . Recently, Boonen et al examined the transdermal kinetics of seven kinds of mycotoxins, AFB1, OTA, FB1, citrinin (CTN), zearalenone (ZEN) and T-2 toxin, using human skin in an in vitro Franz diffusion cell setup 19 , and they reported that except for FB1, all mycotoxins penetrate through the skin and that OTA shows the highest penetration 19 .…”

Section: Introductionmentioning

confidence: 99%

“…However, during the last decade, several researchers have added more information on dermal toxicity and/or tumorigenesis induced in mice by topical application of AFB1 15 , patulin (PAT) 26 , 27 , CTN 12 and OTA 28 , 29 . This paper reviews the molecular mechanisms of dermal toxicity and tumorigenesis experimentally induced in mice or rats by T-2 toxin, CTN, PAT, AFB1 and OTA especially from the viewpoint of oxidative stress-related pathways.…”

Section: Introductionmentioning

confidence: 99%

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Mechanisms of Mycotoxin-induced Dermal Toxicity and Tumorigenesis Through Oxidative Stress-related Pathways

Doi

Uetsuka

2014

J Toxicol Pathol

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Among the many mycotoxins, T-2 toxin, citrinin (CTN), patulin (PAT), aflatoxin B1 (AFB1) and ochratoxin A (OTA) are known to have the potential to induce dermal toxicity and/or tumorigenesis in rodent models. T-2 toxin, CTN, PAT and OTA induce apoptosis in mouse or rat skin. PAT, AFB1 and OTA have tumor initiating properties, and OTA is also a tumor promoter in mouse skin. This paper reviews the molecular mechanisms of dermal toxicity and tumorigenesis induced in rodent models by these mycotoxins especially from the viewpoint of oxidative stress-mediated pathways.

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“…The oxidative damage caused by AF is considered to be the main mechanism leading to the subsequent hepatotoxicity [56]. AFB1 may disturb the integrity of cell membranes by stimulating phospholipid A2 to initiate lipid peroxidation in cells [57]. Animals fed with AF-contaminated diet sufer from oxidative stress as indicated by the signiicant increment of lipid peroxidation and the signiicant reduction of enzymatic antioxidant such as SOD and GSH-Px [54,58,59].…”

Section: Efects On Oxidative Stress Of Alatoxinmentioning

confidence: 99%

The Effect on Oxidative Stress of Aflatoxin and Protective Effect of Lycopene on Aflatoxin Damage

Yılmaz¹,

Kaya²,

Kisaçam³

2017

Aflatoxin-Control, Analysis, Detection and Health Risks

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Alatoxin (AF) is polysubstituted bifuranocoumarins that are secondary fungal metabolites produced by parasiticus/lavus group of the genus Aspergillus. AF is hepatotoxic, nephrotoxic, mutagenic, teratogenic, genotoxic, and immunotoxic, so the International Agency for Research on Cancer has classiied AF as class I human carcinogen. AF-mediated cell injury may be associated with the release of free radicals, and these radicals initiate lipid peroxidation and a damaging process in biological systems since all cell membranes contain the polyunsaturated faty acids (PUFAs), which are substrates for such a reaction. One of the causes for AF-induced toxicity is the oxidative stress, which leads to the improved generation of reactive oxygen species (ROS) and the oxidative DNA damage. Lycopene, a naturally occurring carotenoid, has drawn a particular atention in recent years because of its high antioxidant activity and free radical scavenging capacity and has been shown to be efective against oxidative stress due to AF. Lycopene blocks Phase 1 metabolic enzymes of AFB such as 3A4, 2A6, and 1A2.

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Skin tumorigenic potential of aflatoxin B1 in mice

Cited by 39 publications

References 29 publications

Topical Application of Ochratoxin A Causes DNA Damage and Tumor Initiation in Mouse Skin

Topical Application of Ochratoxin A Causes DNA Damage and Tumor Initiation in Mouse Skin

Mechanisms of Mycotoxin-induced Dermal Toxicity and Tumorigenesis Through Oxidative Stress-related Pathways

The Effect on Oxidative Stress of Aflatoxin and Protective Effect of Lycopene on Aflatoxin Damage

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