PRINCIPLES OF TOXICOLOGY

11.1 MALE REPRODUCTIVE TOXICOLOGY 211
Figure 11.1 Drawing of seminiferous tubule showing the migration of germ cells to the center during development
and stages of spermatogenesis.
The high rates of cellular division and metabolic activity associated with spermatogenesis are the
basis for susceptibility to certain types of damage. During the duplication of genetic material and cell
division, DNA is particularly vulnerable to damage. In addition, many specialized cellular proteins
and enzymes are needed and a high level of cellular respiration is required. Therefore, chemicals that
can cause DNA damage or interfere with cellular protein function or respiration are of particular
concern in rapidly dividing tissues. Examples include reactive electrophilic chemicals such as alkylating
agents and ionizing radiation.
Many chemicals or their metabolites that are considered to be relatively toxic have the ability to
undergo chemical reactions with DNA or important cellular proteins. Depending on the particular
chemical, DNA damage may result from direct interaction with the strands or with other cellular
macromolecules involved in stabilizing the DNA. Reactions with DNA can affect base pairing and
strand linkage. Protein damage can include modifying enzymes and carrier molecules such that they
cannot participate in biochemical reactions.
Anti-neoplastic drugs used in chemotherapy, such as methotrexate, adriamycin, cyclophosphamide,
vincristine, and vinblastine, are good examples of reactive compounds that can cause failures of germ
cell production. Some examples of reactive chemicals with common occupational or environmental
exposures and particular concerns with regard to rapidly dividing spermatogenic tissues include:
• Acrylamide & ethylene oxide—extensively industrial use
• Polynuclear aromatic hydrocarbons (PAHs)—combustion products
• Ethylene dibromide & dibromochloropropane—fumigants/pesticides