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A n n u a l C o n g r e s s o n
Medicinal Chemistry,
Pharmacology and toxicology
Journal of Organic & Inorganic Chemistry
ISSN: 2472-1123
J u l y 3 0 - 3 1 , 2 0 1 8
Am s t e r d a m , N e t h e r l a n d s
Medchem & Toxicology 2018
Page 22
G
ermline stem cells are extremely sensitive to genotoxic chemotherapeutic
agents which induce DNA damage, and even low doses to the testis may
pose reproductive risks with potential treatment-related infertility. Strand breaks
represent a great threat to the genomic integrity of spermatogonial stem cells,
which are essential tomaintain spermatogenesis and prevent reproduction failure.
The single-cell gel electrophoresis (Comet) assay has been used to measure DNA
damage in male germ cells. We investigated the effects in vitro, of six well-known
genotoxins on rat germ stem cells separated using STA-PUT unit-gravity velocity
sedimentation. N-ethyl-N-nitrosourea (ENU), N-methyl-N-nitrosourea (MNU),
6-mercaptopurine and 5-bromodeoxyuridine, methyl methanesulfonate (MMS)
and ethyl methanesulfonate (EMS) are potent male rodent germcell mutagens. All
compounds were significantly genotoxic in cultured germ cells. Treatment of the
isolated germ cells with ENU and MNU produced a concentration-related increase
inDNAdamage in spermatogonia; spermatocytesweremost sensitive to6-MPand
5-brdU with MMS and EMS most damaging in spermatids. Immunocytochemistry
and western blot analysis revealed that the purities of the isolated germ cells
were 90% with viability over 95%. These results indicate that STA-PUT isolated rat
testicular germ cells are a suitable model to study the genotoxicity of individual
chemicals in germ stem cells and could be used as a surrogate system for
humans. Only sperm can be examined in this way in humans.
Biography
Professor Anderson completed her PhD at the University
of Manchester, UK in the Faculty of Medicine. She is the
Established Chair in Biomedical Sciences at the University of
Bradford. She has published more than 450 papers, 9 books,
successfully supervised 32 PhD students, has a Hirsch index
of 59. She is Editor –in- Chief of a Book Series for the Royal
Society of Chemistry and is a Consultant to many International
Organisations, such as the World Health Organisation/
International Programme of Chemical Safety.
d.anderson1@bradford.ac.ukResponses to well-known genotoxic
agents in germ stem cells
in vitro
D.Anderson, K. Habas, M. Najafzadeh,
A. Baumgartner and M.H.Brinkworth
School of Medical Sciences, University of Bradford, Bradford, U.K
D.Anderson et al, J Org Inorg Chem 2018, Volume 4
DOI: 10.21767/2472-1123-C3-007