Review Article | Open Access

Oday S. Abbas1 , Dalia A. Abdul-Shaheed2 and Rand M. Anwer1

1Ibn Sina University of Medical and Pharmaceutical Sciences, Baghdad, Iraq.
2College of Veterinary Medicine, University of Baghdad, Baghdad, Iraq.
J Pure Appl Microbiol. 2018;12(4):1825-1828 | Article Number: 5283 | © The Author(s). 2018
Received: 13/07/2018 | Accepted: 30/09/2018 | Published: 30/12/2018

Mycotoxins are microbial agents which cause food or feed-borne intoxications. Mycotoxins are undesirable compounds often found in cereal grains and forages. Ochratoxin A (OTA) is mycotoxin creates by more than a few type of Aspergillus in addition to Penicillium and can cause benign and/or malignant tumors. Due to that, this study was planned to induce cancer in mice mammary gland by (OTA). Twenty mice were caged to tow experimental groups and treated (10ppb OTA) for 6 months. The results showed that the mammary gland gross appearance gave enlargement with irregular shape while the histopathological changes showed pleomorphic hyperchromatic malignant cells indication for malignant adenocarcinoma of mammary gland.  These results clearly indicated that OTA has carcinogenic compound that cause cancer in mammary gland of mice.


Mycotoxins, Ochratoxin A, Carcinogenic effects, Fungal contamination.


One of the most contaminants to the natural food is Mycotoxins  it is basically  formed by moulds of Aspergillus genetics in addition to Fusarium spp as weel as Penicillium.

The toxicity effect of Mycotoxins on health of animals and human beings is rising and growing up  and that’s incourage the countries to legislate laws to terminate their existence in food through a very strict control specially Aflatoxins (AFs), Mycotoxins are Ochratoxin A (OTA), Patulin and Fusarium toxins1. Fungi produce this biochemical for a wide array of reasons, many of which remain unknown2. Mycotoxins production tends to increase when fungal growth rates slow down and as fungi move toward dormancy; in such instances, mycotoxins production appears to be a defensive reaction3.

Ochratoxin formed from Mycotoxin in addition to  produced by quite a few types of Penicillium and Aspergillus. Among different types of Ochratoxin, Ochratoxin A is most important, the other being the methyl and ethyl ester of OTA, which is also known as Ochratoxin C and Ochratoxin B4. Numerous evidences proposed to facilitate OTA can cause cancer (carcinogenic) to animals and human beings. Initially OTA cause a nephropathy which can cause death due to its effect on kidneys frailer and diseases, the diseases is called (BEN) Balkan Endemic nephropathy. Subsequently, OTA is consider to be toxic to immune and the genetics to many genus.

Petkova-Bocharova and his coworker (1998) mentioned that in 1993 the cancer research agency (IARC) finished that OTA can cause cancer to human brings (Type 2B) in addition to placenta which damage the DNA as well as the tissues and eventually case fatal and death5. Also The National Toxicology Program  (NTP)6 have recognized 42 chemicals that considered to be the main reason to tumors in mammary gland tumors to animals. The Environmental Risk Factors and the Cornell Program on Breast Cancer and upon a revision and research on those chemical was ended that the contact to those chemicals have a great effect on human health and safety7.

The question addressed in this study is: what is their carcinogenicity risk of OTA assessments in Vivo?

Materials and Methods

This research is a joint research by the College of Veterinary Medicine / University of Baghdad and the Iraqi Center for Cancer and Medical Genetic Research. All chemicals and Standards of OTA were purchased from Sigma.

Animals and experimental design
Twenty female albino BALB/C mice were used in this study, aged 3-4 weeks and weight (15 ± 20) g. supplied by the animal house. They were housed and maintained in a conventional animal facility, with controlled conditions of temperature (18 ± 6ºC) with lighting program of 12 Light and 12 Dark hours. The animals were fed on special formula feed pellets and given tap water.

Throughout the experiments, each ten mice were housed in a plastic cage containing hard-wood chip as bedding. The bedding was changed weekly to ensure a clean environment. Twenty females were separated into 2 groups each group has 10 females. One group was considered as control and it was not treated while the second was exposed to Ochratoxin A (10 ppb) by drinking water for 6 months6.

Histological examination
Tissue processing (mammary gland) and staining depending on8.


Grossly of Mammary gland
The disgusting outward shows a noticeable difference and shape size.

The experiments were achieved on mice and figure 1 below shows the  mammary gland of mice that was exposed to Ochratoxin, the figure indicate clearly the effect of hateful cell as well as the pleomorphic hyper chromatic which indicates the adenocarcinoma.

Fig. 1. Indicate clearly the effect of hateful cell as well as the pleomorphic hyper chromatic which indicates the adenocarcinoma ­(H&E (↑)­ 200 X)

Fig. 2. Mammary gland for mice exposed to Ochratoxin (H&E­­­­­ (↑)­ 200 X)


The study indicate that Ochratoxin A is dangerous, and toxic and can ruin food and also can cause worsen the animal as well as human being health.

To have safe of food,  it is very important to keep the food away from Ochratoxin A and be aware from being contaminated with it, and that’s why it is important to establish a very accurate system to keep the food away from contamination with it. The most important factors that affect the presence of Ochratoxin A are humidity and the temperature those two things has to be well maintained to prevent the exposure of food to Ochratoxin, that’s why the monitoring and good control must achieved to maintain healthy food with no Ochratoxin A9.

Upon the experimental studies, researches and evidences Ochratoxin A sensibly predictable to cause cancer to animals and human being and this was totally approved in the studies achieved on mice and it was found (when mice exposed to Ochratoxin A), it was found that mice will suffer from renal cell tumors and hepatocellular tumors as well as mammary gland tumor in addition to hyper plastic hepatic nodules and hepatomas10.

In 2016 Malir and her coworkers observed that OTA  can be the main reason to smash up DNA, which may lead to creation of cancer in animals and human as well due to the indirect effect of OTA on some of the body processes due to DNA damage which eventually case damage to the cells11.

Experiments achieved on ice indicate that when oral tissues exposed Ochratoxin A, this may cause tissues to be damaged which leads to appear tumors in mice12. In addition to that cancer tumors may appears in kidney, stomach and mammary-gland tumors of female rats as well as male rats13,15.


We appreciate the laboratories of the Iraqi Center for Cancer and Medical Genetic Research its valuable cooperation in this research.

Conflict of Interest
The author(s) declare that there is no conflict of interest.

  1. Reddy, K., Nurdijati, S. and Sallch, B. An Overview of Plant-Derived Products on Control of  Mycotoxigenic Fungi and Mycotoxins. School of Biological Sciences, University Sains Malaysia. Asian Jornal of plant Science., 2010;  9: 126-133.  
  2. Magan, N. and Aldred, D. Post-harvest control strategies: Minimizing mycotoxins in the food chain. International Journal of Food and Microbiology., 2007; 119: 131-139.
  3. Wang, J.,  Zhou, Y., Liu, W., Zhu, X., Du, L. and Wang, Q. Fumonisin level in corn-based food and feed from Linxian Country, a high-risk area for esophageal cancer in China. Food Chemistry., 2010; 106: 241-246.
  4. Murphy, P.A., Hendrich, S., Landgren, C. and Bryant, C.M. Food mycotoxins: An update. Journal of Food Science., 2006; 71: 51-65.
  5. Petkova-Bocharova, T., Stoichev, I., Chernozemsky, I., Castergnaro, M. and Pfohl-Leszkowicz, A. Formation of DNA adducts in tissues of mouse progeny through transplacental contamination and/or lactation after administration of a single dose of ochratoxin A to the pregnant mother. Environmentaland Molecular Mutagenesis., 1998;  32: 155–162.
  6. National Toxicology Program (NTP). Report on Carcinogens. Department of Health and Human Services, Twelfth Edition. 2011.
  7. Breast Cancer and Environmental Risk Factors Program (BCERF). Ochratoxin-A: Its Cancer Risk and Potential for Exposure. Cornell University, Fact Sheet #51. 2004.
  8. Bancroft, J. and Steven, A. Theory and Practical of Histological Techniques. 2nd ed. Churchill Livingstone, London, 111: 189-190. 1982.
  9. Naseem, Z., Nadia, J., Sajid, R., Imran, K. and Muhammad, K. Ochratoxin: A Potent Carcinogen. International Research Journal of Biological Sciences., 2016; 5(11): 21-26.
  10. Majeed, M., Ali, A., Muhammad, A., Aamir, S. and Muhammad, S. Ochratoxin A in Cereal Products, Potential Hazards and Prevention strategies. Pakistan Journal of Food Science., 2013; 23(1): 52-61.
  11. Malir, F., Vladimir, O., Annie, P., Jan, M. and Jakub, T. Ochratoxin A: 50 Years of Research. Toxins., 2016; 8, 191. doi: 10.3390/toxins8070191.
  12. IARC. Ochratoxin A. In Overall Evaluations of Carcinogenicity. IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Humans, suppl. 7. Lyon, France. International Agency for Research on Cancer., 1987; 90: 271-272.
  13. Bui-Klimke, T.R. and Wu, F. Ochratoxin A and human health risk: A review of the evidence. Critical Reviewers in Food Science and Nutrition., 2015; 55(13): 1860-1869.
  14. Mantle, P., Kulinskaya, E. and Nestler, S. Renal tumourigenesis in male rats in response to chronic dietary ochratoxin A. Food Additives Contamination., 2015; 22(1): 58-64.
  15. Murphy, P., Hendrich, S., Landgren, C. and Bryant, C. Food mycotoxins: An update. Journal of Food Science. 2006; 71: 51-65.

Article Metrics

Article View: 1977

Share This Article

© The Author(s) 2018. Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License which permits unrestricted use, sharing, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.