MP7 Toxicogenomics in Environmental Studies
Monday, 14 November 2005: 8:00 AM - 5:30 PM in Exhibit Hall

(CAR-1117-202124) Discovery of Genes Associated with PCB Toxicity and Resistance in Atlantic Tomcod.

Carlson, E¹, Roy, N², Wirgin, I², ¹ University of Southern Mississippi, Ocean Springs, MS, USA² New York University School of Medicine, Tuxedo, NY, USA

ABSTRACT- Several populations of fish inhabiting highly contaminated environments possess heritable resistance to early life stage (ELS) toxicity induced by halogenated aromatic hydrocarbons (HAHs) such as TCDD and co-planar PCB congeners. ELS toxicities induced by HAHs in sensitive fish populations include mortality, widespread circulatory failure, edema, and craniofacial /spinal malformations. The molecular mechanisms behind heritable resistance to HAH toxicity in fish populations are unknown. F1 and F2 generation embryos derived from the Hudson River (HR; New York) population of Atlantic tomcod (Microgadus tomcod) are highly resistant to PCB- and TCDD-induced CYP1A expression and ELS toxicity when compared to tomcod embryos of Miramichi River (MR; New Brunswick, CA) and Shinnecock Bay (SB; New York) origin. This study sought to identify novel genes involved in population differences in embryonic response to PCB exposure using custom cDNA microarrays. Microarray probes consisted of 4,416 un-sequenced inserts of randomly-picked clones from a tomcod cardiac cDNA library. Tomcod embryos from three populations (i.e., HR, MR, and SB) were exposed to 2 doses of an environmentally-relevant PCB mixture and screened for dose- and population-specific patterns of gene expression. Greater than 100 clones were found to be significantly altered within each population for each PCB dose, but < 12 PCB-altered clones were shared between any two populations within each exposure group. In addition, <6 significantly-altered clones were shared between high and low PCB exposure groups within any population. Clones displaying significant differences between populations exposed to the high dose of PCB were chosen for identification by DNA sequencing. Of the 28 identified non-ribosomal protein clones, none displayed expression patterns similar to CYP1A. Both cardiac troponin T2 (tnnt2) and cathepsin L precursor appeared to be slightly induced by the high PCB dose in HR embryos and repressed in MR and SB embryos. Interestingly, previous studies have determined that the zebrafish mutant silent heart lacks tnnt2 expression and displays significant cardiomyopathy. Thus, it appears that the PCB-induced gene expression patterns in sensitive tomcod populations may be related to severe cardiovascular dysfunction.

Key words: Microarray, Fish, PCB, Resistance