6-Nitrochrysene (6-NC) is a potent lung and liver carcinogen in the newborn mouse assay. In this report, we extended our studies of the structure-tumorigenicity relationships of the mononitrochrysene isomers. We synthesized 1-NC, 2-NC and 3-NC by oxidation of the corresponding aminochrysenes with mCPBA; efforts to synthesize 4-NC and 5-NC from 4- and 5-aminochrysene were not successful. The tumorigenic activities of 1-NC, 2-NC, 3-NC and 6-NC were compared. Groups of mice were treated with the appropriate compounds in dimethylsulfoxide (DMSO) by i.p. injection on the 1st, 8th and 15th day of life. At a total dose of 100 nmol/mouse, 6-NC induced significant incidences and multiplicities of lung tumors in mice in both sexes; only males were susceptible to liver tumor induction. At 100 nmol/mouse, induction of lung and liver tumors by 1-NC, 2-NC and 3-NC was not significantly different from that observed in mice treated with DMSO. The results indicate that nitro substitution at the 6-position of chrysene is critical for strong tumorigenicity in the newborn mouse assay.
Bibliographical noteFunding Information:
We thank Dr Jyh-Ming Lin for providing NMR spectra, Mr Stuart Coleman for MS and Dr Jerome Solomon and Kathleen Decker-Samvelian of New York University for high resolution MS measurements. We also thank Ms Laura DiSciorio and Mrs Patricia Sellazzo for preparing this manuscript. The editorial assistance of Mrs Dse Hoffmann is gratefully acknowledged. This study was supported by National Cancer Institute grants no. CA-35519 and CA-44377.