Effects of chronic nicotine administration and age in male Fischer-344 rats

Abstract

The chronic effects of nicotine were studied in male Fischer-344 rats over periods of 2 or 22 months. Nicotine (1000 μg base/ml/kg/day) was given sc in 6% gelatin, whereas control rats received 0.85 g/100 ml w/v NaCl in 6% gelatin. Nicotine-treated rats achieved and maintained a significantly lower ( p < 0.01) weight gain than control animals, and the weight of several tissues in both control and nicotine-treated groups showed a change with age. There was no significant change in hemoglobin, or hematocrit, or mean corpuscular volume, hemoglobin, and hemoglobin concentration, or in red and white blood cell counts between control and nicotine-treated rats. Similarly, the differential white cell count did not differ between the 2 groups; however, an increasing percentage of neutrophil polymorphonuclear leucocytes and a decreasing percentage of lymphocytes was shown for both groups with age. Platelet number and morphology were not altered. Several neoplasms developed in the animals injected for 22 months. Two tumors, an adenocarcinoma of the lung and chromophobe adenoma developed in the 6 old control rats (33%), and 9 tumors (3 instances of pheochromocytoma, 4 cases of epidermoid carcinoma of the skin, 1 rat with leukemia and 1 animal with fibrosarcoma) developed in 8 of the old treated rats (29%). The incidence of Leydig cell hyperplasia differed significantly with lesions developing in 66% of the old control rats compared to 89% of the old treated rats ( p < 0.05). It is possible that the physiologic age of the nicotine-treated rats was significantly greater than the controls, and thus the animals were at greater risk for the development of this lesion. Nicotine administration had no effect on the Ca 2+-dependent myosin ATPase activity or on the lactic dehydrogenase activity and isozyme pattern from predominantly fast (gastrocnemius), slow (soleus) or cardiac muscles. Mg 2+-dependent ATPase activity from soleus muscle myofibrils was considerably depressed after 22 months of nicotine treatment, whereas activity from cardiac and gastrocnemius muscles was unchanged.