Demonstration of in vivo formation of the nitrosamine N-nitroso-N-methylaniline from amyl nitrite

Abstract

Kaposi's sarcoma is associated with Acquired Immune Deficiency Syndrome (AIDS) in U.S. homosexuals. A possible explanation is that butyl nitrite, inhaled as a drug of abuse, initiates the tumor via the in vivo formation of N-nitroso compounds. To demonstrate that such a process can occur, we injected mice i.p. with the amine N-methylaniline (250 mg/kg), gavaged them 30 min later with amyl nitrite (AmNO2, 40 mg/kg), killed the mice after another 30 or 60 min, and analyzed the carcasses for N-nitroso-N-methylaniline (NMA). We obtained 480 +/- 130 (mean +/- S.E. for 6 mice killed after 30 min) and 380 +/- 40 (for 6 mice killed after 60 min) nmol NMA/mouse. Much lower yields were obtained when AmNO2 was injected i.p. and methylaniline was gavaged. Hence, relatively large amounts of at least one nitrosamine can be produced in vivo from simple nitrite esters.