1317 ISSN 0326-2383 KEY WORDS: Apoptosis, DNA damage markers, Doxorubicin, Genistein, Genotoxicity, Human lymphocyte culture. * Author to whom correspondence should be addressed. E-mail: afzal_amu@yahoo.com Latin American Journal of Pharmacy (formerly Acta Farmacéutica Bonaerense) Lat. Am. J. Pharm. 30 (7): 1317-24 (2011) Regular Article Received: April 14, 2011 Revised version: April 25, 2011 Accepted: April 30, 2011 Genistein Suppresses Doxorubicin Associated Genotoxicity in Human Lymphocytes Tanveer BEG 1,2 , Yasir H. SIDDIQUE 1 , Gulshan ARA 1 , Asfar S. AZMI 3 & Mohammad AFZAL 1 * 1 Human Genetics and Toxicology Lab, Department of Zoology, Aligarh Muslim University, Aligarh 202002 (UP), India. 2 Current address: Biology Department, Jazan University, Jazan, Saudi Arabia. 3 Department of Pathology, Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA. SUMMARY. Doxorubicin is a well-known DNA intercalating chemotherapy drug that is widely used for treatment of different cancers. Its clinical utility is limited due to the observed genotoxic side effects on healthy cells suggesting that newer combination and genoprotective regimens are urgently needed for the management of doxorubicin chemotherapy. Some dietary phytochemicals are well known for their protec- tive mechanism of action and genistein from soy is recognized as an anti-oxidant with similar properties. Therefore, the present study investigates the effect of genistein against the genotoxic doses of doxorubicin by assessing chromosomal aberrations, sister chromatid exchanges, cell cycle kinetics, cell viability, apop- tosis, and DNA damage markers in cultured human lymphocytes. Our results reveal that genistein treat- ment significantly suppresses genotoxic damage induced by doxorubicin. It is concluded that genistein has the potential to reduce the genotoxicity induced by anti-cancer drugs, thereby reducing the chances of de- veloping secondary tumors during the therapy. INTRODUCTION Doxorubicin is used to treat various forms of cancer. It is sold under various brand names like Adriamycin, Rubex or Doxil. Doxorubicin is a type of antibiotic that is only used in cancer chemotherapy 1,2 . It slows or stops the growth of cancer cells in the body. The length of treat- ment depends on the types of drugs taken, how well the body responds to them, and the type of cancer. Doxorubicin can cause a decrease in the number of blood cells in the bone marrow. The secondary alcohol and aglycone metabolites of doxorubicin alter metabolism of human erythro- cytes 3 . Prolonged use of doxorubicin can also cause severe heart damage, even years after pa- tient has stopped taking doxorubicin. The risk of heart damage after stopping doxorubicin is higher in children. Many studies have demon- strated the cardiotoxicity potential of doxoru- bicin 4,5 . Doxorubicin induces vascular dysfunc- tion in rat thoracic aorta 6 . Side effects from doxorubicin are common and include nausea and vomiting, loss of appetite, diarrhea, difficul- ty swallowing, thinned or brittle hair, skin irrita- tion or rash, darkening of fingernails or toenails, swelling, pain, redness, or peeling of skin on the palms and soles of the feet 2 . Doxorubicin has been studied for its toxicity using different models and has been proved to be toxic 5,7,8 . The enhanced toxicity potential of a regimen on addition of doxorubicin in combination chemotherapy has been revealed 9 . Genistein is one of several known isoflavones found in a number of plants, with soybeans and soy products being the primary food source. In animal cells, genistein has an- tioxidant and weak estrogenic effect, inhibits ki- nases and modulates cell proliferation and trans- formation 10 . It is synthesized from the flavonone naringenin in leguminous plants through a ring migration reaction catalyzed by the cytochrome p450 enzyme isoflavone syn- thase. It is a precursor in the biosynthesis of an- timicrobial phytoalexins and phytoanticipins in