GLYCEROL ENHANCES 4-NITROQUINOLINE 1-OXIDE-INDUCED PULMONARY TUMORIGENESIS BUT DOES NOT ALTER 4-HYDROXYAMINOQUINOLINE 1-OXIDE-DNA ADDUCT LEVELS IN MOUSE LUNG

抄録

Extending our previous studies, we hypothesized that glycerol enhances 4-nitroquinoline 1-oxide (4NQO)-induced pulmonary tumorigenesis in mice by increasing the metabolic activation of 4NQO to the ultimate carcinogen 4-hydroxyaminoquinoline 1-oxide (4HAQO) in bronchiolar cells. To test this, we examined whether glycerol affects the formation of 4HAQO-DNA adducts in the lung. Sequential changes in the level of total 4NQO and its metabolites in serum and lung tissue were also studied. Male ddY mice were injected subcutaneously with a mixture of [³H]4NQO at a dose of 10mg/kg body weight with or without subsequent administration of 5% glycerol solution as drinking water for a fixed period, and the radioactivity in each compartment was determined sequentially until the end of the 7th week. The results showed that 1) glycerol did not alter either level or the pattern in change of the amount of 4NQO and its metabolites in serum, lung tissue, and lung DNA. 2) the DNA adduct, which was rapidly reduced during the first week, remained constant (1 adduct/10⁶ nucleotides) after the 3rd experimental week, and 3) radioactivity was detected almost exclusively in DNA after the 4th experimental week. It is concluded that enhancement of 4NQO-induced murine pulmonary tumorigenesis by glycerol is not associated with the amount of 4NQO-DNA adducts in the lung.