Effects Of B(a)p On Development And Behavior Of Nematode And The Molecular Mechanism

Benzo(a) pyren[B(a)P],a member of Polycyclic Aromatic Hydrocarbons (PAHs),is widespread environmental and has carcinogenic and mutagenic effects.It can accumμlate in the body of humans and may cause tumors.Though taken as a well studied model for the carcinogenicity,the toxicity of B(a)P on reproduction and development has not been elucidated.As such,most of the results are based on the in vitro experiments and less in vivo outcomes are reported.Here,we used C.elegans as an animal model to investigate the effects of B(a)P on the reproduction,larval development and locomotion of this organism.In addition,the activity changes of the enzymes involved in the antioxidant defense systems were tested.We also employed RNAi technique to explore the function of MAPK pathway-related genes in presence of B(a)P.Based on this work further studies are available to investigate the molecular mechanism of the reflection of B(a)P on animal development,as well as the physiological role of divers signal transduction pathways in this process.In the present work,the amount of eggs produced by C.elegans adults was significantly reduced after exposure of 10μM B(a)P.1-10μM B(a)P impressively repressed the progression of larval development,resulting in growth delay,reduced mature worms and smaller size of adults.And these phenotypes were B(a)P concentration-related.Moreover,B(a)P also induced the abnormal locomotion of the worms which consequently exhibited disorderly movement tracks.Enzyme activity analysis revealed that the activities of GST,SOD,CAT and T-AOC were all signicantly altered after exposure to B(a)P.The GST activities were generally induced at early stage and decreased in the late stage,1μM B(a)P had little effects on the activities of SOD and T-AOC,however,5 and 10μM B(a)P promoted the activities of SOD and T-AOC,and then inhibited them.The CAT activities were repressed at all times,especially when the worms were exposed to higher dose of B(a)P.When the expression of mpk-1(a component of ERK pathway) was repressed by RNA interference,the larval development delay caused by exposure to 10μM B(a)P was partially rescued and the percentage of adults was promoted by 15%.Furthermore, lost function of sek-1 or pmk-1(p38 pathway-related) resulted in a 25%-elevated percentage of adults and a faster larval development than the control worms.It implied that the ERK and p38 pathway played an important role in the B(a)P-induced larval development delay.However,repression of the expression of jnk-1 and mek-1 didn't make any changes to the larval development delay,indicating that another subgroup of MAPK superfamily—JNK pathway was not invovled in this process in C. elegans.