AGE-DEPENDENT CHANGES IN PREVALENCE, SIZE AND PROLIFERATION OF ARTERIAL LESIONS IN COCKERELS .2. CARCINOGEN-ASSOCIATED LESIONS

  • 1 January 1981
    • journal article
    • research article
    • Vol. 9  (5) , 382-393
Abstract
Age-dependent changes were determined in the prevalence, frequency, size and proliferative activity of aortic lesions arising in cockerels injected weekly with the polycyclic hydrocarbon carcinogen 7,12-dimethylbenz(a)anthracene (DMBA). Starting at 4 wk of age, groups of 6 animals received weekly i.m. injections of DMBA (10 mg/kg body weight) dissolved in dimethylsulfoxide (DMSO). Controls were injected with DMSO. Animals were sacrificed at 4 wk intervals between 8-20 wk of age. Microscopic lesions were observed in the abdominal aortas of all animals regardless of age or treatment. At no time point were there statistically significant differences in the prevalence or frequency of lesions between DMBA-treated animals and age-matched controls. Lesion areas were log-normally distributed in all groups. DMBA exposure elicited 2 sets of changes not seen in controls. Carcinogen treatment accelerated the time and rate of appearance of large lesions. Eight week old DMBA-treated animals displayed lesion sizes comparable to those seen in 20 wk old controls. Continued exposure to DMBA resulted in sharp increases in lesion size up to 20 wk of age. Between 12-20 wk lesion size increased in a nearly linear fashion by 12 .times. in DMBA-treated animals but only by 2 .times. in controls. There was a burst of lesion cell proliferation in cockerels after 12 wk of DMBA treatment that was not seen in controls or in medial cells of either experimental or control animals. Chronic carcinogen exposure apparently results in the accelerated development of pre-existing spontaneous lesions rather than the initiation of new lesions. Within a lesion there may exist subpopulations of cells which are more capable of proliferating in response to DMBA, and presumably to other agents, than are the majority of lesion cells.

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