Alterations in DNA and cell membranes in an initiation process of carcinogenesis by N-nitrosourea.
We examined DNA alkylation of rat organs (liver, stomach, kidney, lung, and brain) treated with a tissue specific carcinogen, N-methyl-N'-(beta-naphthyl)-N-nitrosourea (MNaNU) (200 mg/kg wt.). There is no correlation between the level of O6-methylguanine (O6-MeG) and formation of tumors with these organs. Fourier-transform infrared (FT-IR) spectra of the treated tissues were compared with those obtained form the non-treated organs in the region between 1000 and 1350 cm-1. The infrared spectra of the treated stomach which is a target organ for induction of tumors showed the formation of hydrogen bonding in carbohydrates, disturbance of nucleic acid structures, and presence of disordered states in the membranes. Further, the stomachs were divided into the forestomachs (target tissue) and glandular stomachs, and their FT-IR spectra were also examined. Using 1134 cm-1 band due to the C-H plane bending of the naphthyl ring of MNaNU, we estimated approximately 0.82 mg of MNaNU would persist in the forestomach of one rat at 6h after administration. The present results demonstrate importance of pharmacokinetics and receptor sites in cell membrane in addition to DNA alkylation for carcinogenesis by directly acting N-nitroso compounds.
Yano
K
K
Department of Chemistry, Saitama Medical School, Japan.
Katayama
H
H
Sonoda
M
M
Skagishi
Y
Y
Niimi
S
S
D000477:Alkylating Agents / Q000633:toxicity*; D000478:Alkylation; D000818:Animals; D001665:Binding Sites; D002273:Carcinogens / Q000633:toxicity*; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects; D004247:DNA / Q000737:chemistry / Q000187:drug effects*; D006147:Guanine / Q000031:analogs & derivatives / Q000737:chemistry; D006860:Hydrogen Bonding; D008297:Male; D008770:Methylnitrosourea / Q000031:analogs & derivatives* / Q000633:toxicity; D009374:Neoplasms, Experimental / Q000139:chemically induced*; D009928:Organ Specificity; D051381:Rats; D017208:Rats, Wistar; D017550:Spectroscopy, Fourier Transform Infrared; D013270:Stomach / Q000737:chemistry / Q000187:drug effects
D000477:Alkylating Agents; D002273:Carcinogens; D006147:Guanine; D008770:Methylnitrosourea; D004247:DNA; C008449:O-(6)-methylguanine