Involvements of cyclic nucleotide systems in enlarged mice lungs produced by butylated hydroxytoluene

A single intraperitoneal injection of butylated hydroxytoluene (BHT), at a dose of 400 mg/kg of body weight, to mice caused enlargement of their lungs, which was found to be associated with some modifications in certain parameters of the cyclic nucleotide systems. These include: (a) increased levels of cyclic GMP, with cyclic AMP levels remaining unaffected, (b) increased levels of phosphodiesterases for cyclic GMP and cyclic AMP, with the lowest ratio of these activities seen at the beginning of the tissue mass increase, (c) increased levels of both cyclic GMP-dependent and cyclic AMP-dependent protein kinases, and (d) increased levels of stimulatory modulator of the cyclic GMP-dependent enzyme, with unaltered levels of inhibitory modulator of the cyclic AMP-dependent enzyme. Since increases in levels of cyclic GMP, the cyclic GMP target enzyme and its stimulatory modulator, as well as of the activity of DNA polymerase, occurred prior to or coincided with the pulmonary hypertrophy and hyperplasia, it is suggested that the cyclic GMP-mediated processes may be particularly crucial for cell proliferation after toxic injury of the lung by BHT.