Acrylonitrile interaction with testicular DNA in rats.
In the present study we report the in vivo interaction of acrylonitrile (VCN) with testicular tissue in rats. Covalent binding of radioactivity to testicular tissue DNA was examined for a period of 72 hr after a single oral dose (46.5 mg/kg) of [2,3-14C] VCN. Maximal covalent binding was observed at 0.5 hr (8.9 mumol VCN equivalent/mol nucleotide). Binding decreased gradually thereafter but was still detected (2.5 mumol VCN equivalent/mol nucleotide) at 72 hr following VCN administration. Further, we examined the effects of VCN on DNA synthesis and repair in the testes of rats following a single oral dose (46.5 mg/kg) of VCN to clarify the impact of the covalent binding observed on the testicular genetic material. A significant decrease in DNA synthesis (80% of control) was observed at 0.5 hr after treatment. At 24 hr following acrylonitrile administration, testicular DNA synthesis was severely inhibited (38% of control). Testicular DNA repair was increased 1.5-fold at 0.5 hr and more than 3.3-fold at 24 hr following treatment with VCN. These results suggest that VCN can act as a multipotent genotoxic agent by alkylating DNA in testicular tissue and may affect the male reproductive function by interfering with testicular DNA synthesis and repair processes.
Ahmed
A E
AE
Department of Pathology, University of Texas Medical Branch, Galveston 77555.
Abdel-Rahman
S Z
SZ
Nour-al Deen
A M
AM
D000181:Acrylonitrile / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D004247:DNA / Q000096:biosynthesis / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012044:Regression Analysis; D013737:Testis / Q000187:drug effects* / Q000378:metabolism
D004247:DNA; D000181:Acrylonitrile