Correlation of regional and nonlinear formaldehyde-induced nasal cancer with proliferating populations of cells

• Published in: Cancer research (Chicago, Ill.) Ill.), 1996-03, Vol.56 (5), p.1012-1022
• Main Authors: MONTICELLO, T. M, SWENBERG, J. A, GROSS, E. A, LEININGER, J. R, KIMBELL, J. S, SEILKOP, S, STARR, T. B, GIBSON, J. E, MORGAN, K. T
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Carcinogenesis, carcinogens and anticarcinogens; Carcinoma, Squamous Cell - chemically induced; Carcinoma, Squamous Cell - pathology; Cell Division - drug effects; Chemical agents; Dose-Response Relationship, Drug; Formaldehyde - toxicity; Male; Medical sciences; Nasal Cavity; Nose Neoplasms - chemically induced; Nose Neoplasms - pathology; Rats; Rats, Inbred F344; Tumors
• ISSN: 0008-5472; 1538-7445

Formaldehyde induces nonlinear, concentration-related increases in nasal epithelial cell proliferation and squamous cell carcinomas (SCC) in rats. A formaldehyde carcinogenicity study was conducted in which a major end point was correlation of cell proliferation indices with sites of formaldehyde-induced SCC. A poor correlation in certain sites led to incorporation of the number of cells in each site into the correlation. Rats were exposed (6h/day, 5 days/week) to formaldehyde (0, 0.7, 2, 6, 10 or 15 ppm) for up to 24 months with interim sacrifice time points at 3, 6, 12, and 18 mo. A unit length labeling index (ULLI; S-phase nuclei/mm basement membrane) was determined for specific nasal regions in addition to a population-weighted ULLI (PWULLI). The PWULLI was defined as the product of regional ULLI and total number of nasal epithelial cells in the respective site. Nasal SCC sites of origin were mapped. Formaldehyde induced SCC in a highly nonlinear fashion, with no observed effect at the level of 2 ppm, a minimal response at 6 ppm, and a sharp increase at 10 and 15 ppm. The tumor incidence was 1, 22, and 47% at 6, 10 and 15 ppm, respectively. ULLI was significantly (P