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In vitro carcinogenesis with cells in early passage
National Cancer Institute Monograph
|May 1, 1978
Summary
In vitro studies demonstrate that chemical carcinogens can induce cancer at the cellular level. These methods rapidly evaluate environmental agents, aiding in the identification of potential cancer-causing chemicals.
Area of Science:
- Cellular and Molecular Oncology
- Environmental Toxicology
- Carcinogenesis Research
Background:
- Cancer induction can be studied at the cellular level, with transformation frequency correlating linearly with dose, suggesting a "one-hit" phenomenon.
- In vitro studies using mammalian cells offer rapid evaluation of environmental agents' carcinogenicity.
- Neoplastic transformation is an inductive process, not a selection of pre-existing tumor cells.
Purpose of the Study:
- To establish practical in vitro methods for identifying environmental chemicals with cancer-producing potential.
- To investigate the interaction between cellular targets and chemical carcinogens.
- To explore how combinations of agents (chemical, viral, radiation) influence cancer risk and develop new surveillance assays.
Main Methods:
- Utilizing in vitro mammalian cell culture systems to quantitate neoplastic transformation.
- Incorporating a host-mediated step in bioassays to reduce false negatives from metabolic activation.
- Employing sequential treatments with chemicals, viruses, and radiation on Syrian golden hamster embryo cells.
Main Results:
- In vitro transformation frequency shows a linear relationship with dose, supporting a "one-hit" model.
- Pretreatment with X-irradiation or methyl methanesulfonate, but not UV-irradiation, enhanced chemical transformation frequency.
- Posttreatment with caffeine also increased chemical transformation frequency.
- Most chemical carcinogens increased hamster embryo cell sensitivity to simian adenovirus SA7 transformation, with enhancement dependent on treatment duration and interval.
Conclusions:
- In vitro methods provide a high probability of practical application for detecting carcinogenic chemicals.
- Understanding cell-target insult interactions and ultimate carcinogen nature is feasible.
- Combinations of carcinogenic agents may increase cancer risk and necessitate novel surveillance assays for environmental agents.