Differences on the level of hepatic transcriptome between two flatfish species in response to liver cancer and environmental pollution levels

Environmental factors can cause cancer in both wild animals and humans. In ecological settings, genetic vari-ation and natural selection can sometimes produce resilience to the negative impacts of environmental change. An increase in oncogenic substances in natural habitats has therefore, unintentionally, created opportunities for using polluted habitats to study cancer defence mechanisms. The Baltic and North Sea are among the most contaminated marine areas, with a long history of pollution. Two flatfish species (flounder, Platichthys Jesus and dab, Limanda limanda) are used as ecotoxicological indicator species due to pollution-induced liver cancer. Cancer is more prevalent in dab, suggesting species-specific differences in vulnerability and/or defence mech-anisms. We conducted gene expression analyses for 30 flatfishes. We characterize between-and within-species patterns in potential cancer-related mechanisms. By comparing cancerous and healthy fishes, and non-cancerous fishes from clean and polluted sites, we suggest also genes and related physiological mechanisms that could contribute to a higher resistance to pollution-induced cancer in flounders. We discovered changes in transcriptome related to elevated pollutant metabolism, alongside greater tumour suppression mechanisms in the liver tissue of flounders compared to dabs. This suggests either hormetic upregulation of tumour suppression or a stronger natural selection pressure for higher cancer resistance for flounders in polluted environment. Based on gene expression patterns seen in cancerous and healthy fish, for liver cancer to develop in flounders, genetic defence mechanisms need to be suppressed, while in dabs, analogous process is weak or absent. We conclude that wild species could offer novel insights and ideas for understanding the nature and evolution of natural cancer defence mechanisms.

Automated summary

Environmental factors can cause cancer in both wild animals and humans. The use of polluted habitats provides opportunities to study cancer defense mechanisms, which can be influenced by genetic variation and natural selection. Flatfish species, specifically flounders, show higher resistance to pollution-induced cancer compared to dabs, with elevated pollutant metabolism and stronger tumor suppression mechanisms in their liver tissue. This suggests a potential hormetic upregulation of tumor suppression or stronger natural selection pressure for cancer resistance in flounders. Wild species offer valuable insights into understanding the nature and evolution of natural cancer defense mechanisms.