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Oncogene activation in experimental carcinogenesis: the role of carcinogen and tissue specificity
1Department of Environmental Medicine, New York University Medical Center, NY 10016.
Abstract:
Techniques of molecular biology have been used to determine the relationship of cellular oncogenes to mechanisms of experimental carcinogenesis. Model systems involving three direct-acting alkylating carcinogens, two organ sites, and two species have been employed to elucidate the relationships between carcinogenic etiology, tissue specificity, and activation of known and novel oncogenes. Dimethylcarbamyl chloride, a reactive acylating agent, induces tumors of both the rat nasal mucosa and mouse skin whose DNA is devoid of NIH 3T3 transforming activity. Beta-propiolactone-induced rat nasal carcinomas contain a novel oncogene, 6 to 9 kb in size, whereas a mouse skin carcinoma induced by this agent possesses an H-ras oncogene activated by a 61st codon A to T transversion mutation. The novel oncogene activated in rat nasal tumors induced by beta-propiolactone is distinct from one found in methylmethane sulfonate-induced tumors. The implications of these findings for understanding how oncogenes fit into general mechanism of carcinogenesis are discussed.
Insights
Carcinogen exposure activates cellular oncogenes, influencing cancer development. Different carcinogens and tissues activate distinct oncogenes, revealing varied carcinogenesis mechanisms.
Area of Science:
- Molecular biology
- Carcinogenesis research
- Oncogene activation
Background:
- Cellular oncogenes play a role in cancer development.
- Understanding oncogene activation is key to understanding carcinogenesis.
- Experimental models are crucial for studying carcinogen-tissue interactions.
Purpose of the Study:
- To investigate the relationship between carcinogens, tissue specificity, and oncogene activation.
- To identify novel oncogenes involved in experimental carcinogenesis.
- To elucidate the mechanisms by which carcinogens induce tumors.
Main Methods:
- Utilized molecular biology techniques.
- Employed model systems with three direct-acting alkylating carcinogens (dimethylcarbamyl chloride, beta-propiolactone, methylmethane sulfonate).
- Studied two organ sites (rat nasal mucosa, mouse skin) and two species (rat, mouse).
Main Results:
- Dimethylcarbamyl chloride induced tumors lacking NIH 3T3 transforming activity.
- Beta-propiolactone induced rat nasal carcinomas with a novel, 6-9 kb oncogene.
- Beta-propiolactone-induced mouse skin carcinomas showed H-ras oncogene activation (A to T transversion at codon 61).
Conclusions:
- Carcinogen-induced oncogene activation varies by carcinogen and tissue.
- Novel oncogenes are implicated in rat nasal carcinogenesis.
- Findings contribute to understanding oncogene roles in general carcinogenesis mechanisms.