Anatomical and functional vascular changes in hamster cheek pouch during carcinogenesis induced by 7, 12-dimethylbenz(a)anthracene.

ABSTRACT

Anatomical and functional vascular changes during hamster cheek pouch carcinogenesis were studied by light microscopy; scanning electron microscopy of vascular casts; transmission electron microscopy of cheek pouch capillaries; and fractional distributions of 51Cr-erythrocytes, 125I-human serum albumin, and 86RbCI which were used to determine vascular volume, permeability, and perfusion. Histopathological changes and focal capillary changes in vascular casts were measured quantitatively by an image analyzer. Male Syrian hamsters received 0.5% 7,12-dimethylbenz[a]anthracene (DMBA) in mineral oil for 11 weeks and were sacrificed at periodic intervals from 2 to 20 weeks after initial treatment. Simple hyperplasia was first seen at Week 1. The area of hyperplastic epithelium, expressed as percentage, increased to about 60% by Week 8 and then decreased to 30% at Week 20. Dysplastic foci were first seen at Week 2. The percentage of the area of dysplasia increased with time to 41% at Week 20. Squamous cell carcinomas occurred from Week 10, increased with time, and were found in all animals at Week 20. Vascular cast diameters of normal-looking capillaries were larger during than after DMBA treatment. Type 3 vascular proliferations were found beneath dysplasia and cancer. Capillaries beneath simple hyperplasia and type 3 capillaries beneath dysplasia and cancers were dilated but not fenestrated. Changes in vascular volume were independent of changes in permeability and perfusion and also occurred in contralateral untreated pouches of treated animals. While 86Rb values initially correlated with 125I values, the 86Rb values were unstable in intermediate and later time periods. Changes of vascular volume were accompanied initially by the presence of DMBA and were coincident with increased areas of dilated capillaries beneath simple hyperplasia and later with areas of type 3 capillary proliferation beneath dysplasia and cancer. Changes of vascular permeability were related to inflammation indices throughout the study. DMBA may lastingly alter capillary endothelium in a manner which allows or aids in its subsequent dilatory and proliferative responses to angiogenic stimulation from malignant tumors, and possibly from premalignant or malignantly transformed cells.