Chemical carcinogenesis – Ulla Stenius' group

We analyze sex differences in response to carcinogens and the carcinogenic effects of silica. The goal of the projects is to improve the scientific base for risk assessment.

Projects

 

Gender differences in chemical carcinogenesis
Men get more cancer than women and understanding this gender difference may lead to means to reduce the cancer burden by 30%. The reason for this difference is largely unknown. In this project we investigate sex differences in response to carcinogens. The specific purpose is to investigate how variable androgen receptor activity affect environmental carcinogen-induced DNA damage in stem cells and its possible role for cancer susceptibility. We also aim to identify chemicals exhibiting sexual dimorphism in their response.

This project is funded by Formas

Cancer risk associated with low dose silica exposure
The overall aim of this project is to characterize mechanisms for silica-induced inflammation and DNA damage at low doses. In cell studies we have found that silica particles induce inflammation and DNA damage in lower doses than previously employed. The finding that this occurs in epithelial cells suggests that this may have a direct bearing on silica-related lung cancer. Our data challenges the mode of action for silica carcinogenesis and suggests that cancer should be seen not as a sequel of silicosis but rather as process that develops in parallel with silicosis. In this project, an alternative type of DNA damage mechanism will be studied. We have found that silica particles cause double strand breaks and micronuclei through activation of endonuclease G. The mechanism will be further characterized in experimental models and its relevance to cancer development investigated. The project may lead to a simplified risk assessment of silica and perhaps also to a lowering of occupational exposure limits.


This project is funded by AFA försäkring

 

Publications

Selected publications

Members and contact

Group leader

All members of the group

Visiting address

Karolinska Institute, Institutet för Miljömedicin, Nobels väg 13, Stockholm, 17177, Sweden

Postal address

Karolinska Institute, Institute of Environmental Medicine, Box 210, Stockholm, 17177, Sweden