Quantitative biochemical markers of DNA hyperploidy as end-point indicators in chemical risk assessment and chemoprevention studies.
Hurst-RE; Rhodes-SW; Petrone-RL; Bas-RA; Hemstreet-GP; Detrisac-CL; Thomas-C; Moon-RC; Kelloff-GJ
Biol Monit 1991 Jan; 1(1):5-15
The usefulness of quantitative fluorescence image analysis (QFIA) as a biological monitoring tool to measure DNA content in bladder wash cells taken from rats treated with N-butyl-N-(4- hydroxybutyl)nitrosamine (3817116) (OHBBN) was investigated. OHBBN was administered at 100mg twice a week for 8 weeks to 143 Fischer- 344-rats. Of these 143 animals, 36 also received 4- hydroxyphenylretinamide (4-HPR). Animals were sacrificed 6 months after the final dose. There was a small shift toward less invasive tumors in the 4-HPR treated animals, but large differences were noted in the cytological characteristics of the cells, reflecting treatment with carcinogen and retinoid. The mean DNA content in the cells classified as nonnormal was shifted toward more normal values when the rats had also received 4-HPR treatment. The mean DNA content shifted from 10.9C to 5.9C in those cells which were visually suspicious, with 2C being a normal cellular DNA content. The shift from a mean DNA content of 4.4C to 3.7C was noted in visually atypical cells. The authors conclude that there are very distinct differences in the ploidy and cytologic characteristics of the cells detected by acridine-orange fluorescence which can be ascribed to an effect of the retinoid in normalizing the cells. This information may point to the development of more accurate and sensitive markers for monitoring the effects of carcinogens and chemopreventive agents.
NIOSH-Grant; Cancer; DNA-damage; Cytotoxic-effects; Carcinogens; Carcinogenesis; Risk-analysis; Epidemiology; Biological-monitoring
Urology University of Oklahoma Dept of Urology, PO Box 26901 Oklahoma City, OK 73190
University of Oklahoma Hlth Sciences Ctr, Oklahoma City, Oklahoma