Abstract
The number of malignant diseases is increased worldwide and people diagnosed with cancer currently have a high chance of survival as a result of new treatment protocols such as surgery, combination chemotherapy and radiation therapy. Maintenance of health is an important key to profitable farm mammalian reproduction. Therefore, keeping newborns alive and healthy may be the greatest management challenge facing farm owners. Important strategies for meeting these challenges include making sure that the reproduction and fetus are in good condition throughout the pregnancy period. It is clear that cytotoxic therapy such as certain chemotherapy drugs influences spermatogenesis at least temporarily and in some cases permanently.
Busulfan Complex
Busulfan (Bu) is an anti-cancer drug, which has been used against chronic myeloid leukaemia (CML) since 1959 and was conventionally used in a low dose over a long period of time in the palliative treatment of CML. Bu was the leading chemotherapeutic treatment for this malignancy. The US Food and Drug Administration (FDA) approved Busulfan as a treatment for CML in 1999. Bu has a very narrow therapeutic index, and acute toxicity may be related to absorption and disposition of the drug and metabolites [1].
Bu, 1, 4-bis [methanesulfony1-y] butane, is a bi-functional alkylating agent and lipophilic molecule that, as soon as systematic absorption, carbonium ions are rapidly formed, resulting in alkylating DNA and leads to breaks in the DNA molecule, following replication and transcription of RNA.
Busulfan and Reproduction
In general, spermatogenesis is a coordinated course begins with spermatogonial proliferation followed by differentiation, such that production of spermatozoa is continuous. Another method is the administration of Bu; as a DNA-alkylating agent, Bu can act on the G0/G1 phase of the cell cycle and arrest the proliferation of germ cells [2], resulting in apoptosis and a decrease in spermatogenesis [3]. Intraperitoneal injections of busulfan have been used to prepare recipients for the transplantation of spermatogonial stem cells [4] and to prepare azoospermia models [5]. This unique recipient preparation method has been in use for several decades because of its many advantages.
The unpredictable pharmacology of Bu in important: several investigators have reported that following use of Bu impotence or irreversible loss of fertility can occur [6-8] and finally may be accurse delayed pubertal development.
Busulfan
Molecular formula
C6 H14 O6 S2
Molecular weight
246.3 Dalton
Color
White-crystalline powder
Soluble
Water/alcohol
Terminal half life (h)
2.3-2.6
Storage °C
Tablets
12-25
Vials
2-8
Table 1: Busulfan.
Figure 1: Replication and Transcription of RNA.
Bu is a potent agent that preferentially kills spermatogonial stem cells of several species; however, it has no effects on DNA synthesis. However, it inhibits the next mitosis when it intoxicates the cells in the G1 phase [3].
Conclusion
In conclusion, Bu consumption for cancer therapy has long-term consequences including reduced fertility and sometimes sterility.
Acknowledgement
The authors wish to acknowledge the excellent work of Gholamali Moghaddam, Behzad Baradaran and Gholamreza Hamidiyan, as well as that of the Immunology Research Center, Tabriz University of Medical Sciences, Iran, that has provided excellent assistance with the preparation of this review.
References
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- Marcon L, Zhang X, Hales BF, Robaire B and Nagano MC. Effects of chemotherapeutic agents for testicular cancer on rat spermatogonial stem/ progenitor cells. J. Androl. 2011; 32: 432–443.
- Brinster RL, and Avarbock MR. Germline transmission of donor haplotype following spermatogonial transplantation. Proc. Natl Acad. Sci. USA. 1994; 91: 11303–11307.
- Smith RP, Lowe GJ, Kavoussi PK, Steers WD, Costabile RA, Herr JC, et al. Confocal fluorescence microscopy in a murine model of microdissection testicular sperm extraction to improve sperm retrieval. J. Urol. 2012; 187: 1918–1923.
- Busulfan. USP DI. Volume 1. Drug information for the health care professional. 20th ed. Englewood, Colorado: Micromedex, Inc. 2002.
- McEvoy G. American Hospital Formulary System Drug Information. Bethesda: American Society of Health System Pharmacists. 2003.
- Repchinsky C. Compendium of Pharamcueticals and Specialties. Ottawa, Ontario, Canada: Canadian Pharmacists Association. 2003.
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