The Incidence of Pulmonary Tumors in Mice Exposed to Aerosols of Therapeutic Agents

An Evaluation of the Possible Carcinogenic Properties of Penicillin, Pyribenzamine, Adrenalin, Cortisone, Trypsin and Desoxyribonuclease

¹ The University of California, School of Medicine, San Francisco, California., University Hospital, Ann Arbor, Michigan.

1. The steadily rising incidence of cancer of the lung indicates that any drug found to have carcinogenic effects in animals should be used with caution in the treatment of pulmonary disease in man. The present investigation was undertaken to determine possible carcinogenic properties of therapeutic agents, as evidenced by the development of pulmonary tumors in mice.

2. Penicillin, pyribenzamine, adrenalin, cortisone, trypsin, and desoxyribonuclease were administered by aerosol inhalation to groups of mice. Strain A mice were used because of the reliable incidence of spontaneous pulmonary tumors in this strain. Treatment was carried out over 10 to 23 week periods; the animals were sacrificed at six and nine months of age.

3. The tumors that developed in all groups were typical of the adenoma that occurs spontaneously in strain A mice. The histologic appearance of the tumors suggested that they originated from the alveoli.

4. The animals treated with cortisone and with desoxyribonuclease for 10 weeks and sacrificed at six months of age showed a statistically significant increase in tumors. The incidence was 26 per cent and 30 per cent, respectively, whereas the reported incidence of spontaneous tumors in 6-month-old strain A mice is 17 per cent. The action of trypsin appeared to be inhibitory, as evidenced by the lower than normal incidence of tumors in the 9-month-old animals treated with this agent. The occurrence of tumors in the animals given the other test drugs was within the normal range.

5. Although no definite conclusion can be drawn at this time, it is postulated that desoxyribonuclease and cortisone may act as co-carcinogens and influence the development of a viral-induced pulmonary adenoma in the strain A mouse.