A new approach to analysis of cell proliferation activity in N-nitrosodiethylamine (DEN) induced hamster tracheal tumorigenesis.

Abstract

Forty-five male Syrian golden hamsters out of 90 were given subcutaneous injections with N-nitrosodiethylamine (DEN) in saline twice a week for 20 weeks to induce tracheal hyperplasia and papilloma. These proliferative lesions were analysed by mitotic index (M.I.) and bromodeoxyuridine-labelling index (BrdU-L.I.), as well as by nucleolar organizer regions (NORs) count to determine the relationship between cell proliferation and (the tumorigenic process.) the tumorigenic process. Besides, the meaning and significance of NORs count was evaluated from the counts in the basal area of the lesions in comparison with M.I. and BrdU-L.I.. The mean M.I., BrdU-L.I., and NORs count in various tracheal lesions were as follows: 0.10%, 0.37%, and 2.12 in control tracheal epithelium, 0.25%, 2.50%, and 2.30 in non-lesional area, 0.37% (0, 27%), 2.15% (3.49%), and 2.33 (2.53) in hyperplasia, 0.23% (0.25%), 3.54% (5.65%), and 2.59 (2.97) in papilloma, respectively. Numbers in the parentheses indicate the values of the basal area. The elevation of NORs count surely reflected the high frequencies of proliferation in the preneoplastic and neoplastic changes as demonstrated by M.I. and BrdU-L.I., but in papilloma increased protein synthesis without cell division was indicated. These results showed that measurement of cell proliferation activity in the basal area could demonstrate the growth rate much more clearly than that in the whole area. Also, it was shown that analysis of distribution patterns of the NORs counts was a useful means for evaluating the biological behavior of the neoplastic lesions.