Modification of lung tumor growth by hyperoxia

Abstract

The effects of hyperoxia on lung tumor development were examined in mice and rats. In mice, exposure to 70% O2 prevented the development of urethan- or 3-methylcholanthrene-induced lung tumors. Dietary antioxidants [butylated hydroxytoluene (BHT) and butylated hydroxyanisole (BHA)] were unable to prevent the inhibition of tumor development by oxygen, although BHT retained its capability to enhance tumor development in mouse lung. In visible-size tumors, oxygen did not depress DNA synthesis. Oxygen also reduced the number of pulmonary metastatic nodules after i.v. injection of mammary gland-derived carcinoma cells, but failed to inhibit growth of murine lung carcinoma or murine melanoma-derived cell lines. Rats treated with one single intratracheal instillation of 3-methylcholanthrene developed multiple lung lesions; their growth could be prevented by exposure of the animals to 40 or 70% O2. It is concluded that hyperoxia prevents development of transformed cells in vivo in the lung and may affect adversely the growth of selected cell lines metastatic to the lung.

Responses of the Lung to Toxic Injury

“…Exposure of such animals to an atmosphere of 70% or even of 40% oxygen dramatically reduced tumor formation (65). The percentage of tumor-bearing rats in the oxygen group was less than half of that found in controls (where practically all animals developed squamous cell carcinomas).…”

“…Sustained exposure to oxygen is able to elicit a continuing cell proliferation in the TIype II cell population of the lung two to four times over basal rate (62). Thus, one might expect that such an event would increase tumor development in the lung, should cell proliferation be such a crucial event in carcinogenesis.…”

“…Reactive oxygen species are believed to be of crucial importance in tumor promotion (63,64). However, in several experiments it was shown that chronic hyperoxia, rather than enhancing tumor development, severely curtails tumor formation in mouse lung-even in the continued presence of an active proliferative response in the lype H cell population and an increased activity of pulmonary ornithine decarboxylase, believed to be a hallmark of tumor promotion (62,65). It has not been possible to apply some mechanistic considerations developed for mouse skin to the mouse lung tumor system.…”

“…A good correlation has been found between rates of basal Type II cell proliferation and the apparent sensitivity of various mouse strains to develop spontaneously occurring lung tumors (66). And although both oxygen (62) or ozone (67) inhibit the development of chemically induced tumors in mice pretreated with a carcinogen, both gases increase the average number of tumors and the percentage of tumor-bearing individuals in mice not knowingly exposed to a carcinogenic agent (62,67,68). This, of course, could imply both ozone or oxygen as pulmonary carcinogens, at least in mice.…”

“…Oxygen appears to have high cytotoxicity for newly transformed tumor cells in mouse lung, and the gas appears to be capable of preventing individual tumor cells or small clusters of transformed cells from growing into visible tumors (62). If this is true, oxygen should prevent tumor development in other species.…”