1,3-Dinitrobenzene metabolism and toxicity in seminiferous tubules isolated from rats of different ages.
Previous in vivo studies in rats have shown that susceptibility to 1,3-dinitrobenzene (DNB)-induced testicular damage increases with age. The present study has used an in vitro approach to investigate the possibility that differences in testicular metabolism contribute to the age-related differences in toxicity. Seminiferous tubules were isolated from Sprague-Dawley rats (30, 75 and 120 days old) and incubated with 100 microM DNB for 22 h. Formation of metabolites and tubular levels of ATP and glutathione (GSH) were monitored over time. There was no difference in seminiferous tubule metabolic capacity among the three ages of rats examined. After 22 h of incubation with DNB, ATP levels were 20-30% of control and GSH levels were 70-90% of control, but neither parameter showed an age-related difference in decline. Based on these biochemical indicators of cell health, this study would suggest that the lack of testicular toxicity in young animals in vivo may be due to the previously described shorter half-life with consequent reduced exposure of the testis to DNB and that the age-related increase in severity of lesion between 75 and 120 days of age cannot be explained by differences in tubular metabolism of DNB or whole-animal toxicokinetics.
Jacobson
C F
CF
Department of Environmental Toxicology, University of California, Davis 95616-8588, USA.
Miller
M G
MG
D000255:Adenosine Triphosphate / Q000378:metabolism; D000375:Aging / Q000502:physiology*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003470:Culture Media; D046508:Culture Techniques; D004136:Dinitrobenzenes / Q000378:metabolism* / Q000633:toxicity; D005978:Glutathione / Q000378:metabolism; D008297:Male; D010100:Oxygen / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012671:Seminiferous Tubules / Q000187:drug effects / Q000378:metabolism*; D013737:Testis / Q000187:drug effects / Q000378:metabolism*
D003470:Culture Media; D004136:Dinitrobenzenes; D000255:Adenosine Triphosphate; C017906:3-dinitrobenzene; D005978:Glutathione; D010100:Oxygen