Mutagenicity testing of selected analgesics in Ames Salmonella strains

Abstract

Acetaminophen (APAP), aspirin (ASA), phenacetin (PA) and ibuprofen (IB) were tested for mutagenic activity in the Ames Salmonella plate incorporation assay using strains TA98, TA100, TA1535, TA1537 and TA1538. These analgesics were tested in four separate tests: without metabolic activation, and in the presence of a rat, hamster or mouse liver post-mitochondrial supernatant (S-9, Aroclor 1254-induced). Treatment of all five strains of Salmonella with APAP, ASA or IB under all four metabolic conditions did not induce any appreciable increases in revertant colony counts, as compared to the negative controls. A dose-related increase in revertant colony counts, reaching levels twice the negative control values, were seen with PA at doses greater than or equal to 500 micrograms per plate. This response was only seen in strain TA100 in the presence of hamster S-9. Therefore, these findings constitute a positive result for PA in the Ames test. APAP, ASA and IB did not show any mutagenic potential under these conditions of testing. These findings are discussed along with previously published results concerning the genotoxicity of these analgesics.

In vitro genotoxic assessment of xenobiotic diacylglycerols in an in vitro micronucleus assay

“…[Parry and Sors, 1993;Gibson et al, 1995;Parry et al, 2002a,b]. The results of this micronucleus assay in vitro demonstrate the aneugenic activity of ibuprofen-DG, Ibuprofen itself has been found nonmutagenic in earlier studies using Ames test and weakly genotoxic in vivo in mice [Oldham et al, 1986;Philipose et al, 1997], and did not increase chromosomal aberrations in blood lymphocytes [Shvarts et al, 1984] which means this drug is nongenotoxic but when it is present in the form of xenobiotic diacylglycerols, then these conjugates can produce genotoxic effects.…”

Investigation of flurbiprofen genotoxicity and cytotoxicity in rat bone marrow cells

“…It has been reported that flurbiprofen did not cause genotoxic effect in peripheral blood cells of human who used flurbiprofen for two weeks (Kullich & Klein, 1986). Although previous studies showed that profens did not cause genotoxic effect (Oldham et al, 1986;Williams et al, 1989), they induced cytotoxicity in some studies (Kim et al, 2004;Parolini et al, 2009). Also, it has been reported that flurbiprofen had scavenging effect on reactive oxygen and nitrogen species (Costa et al, 2006) and various effects on the antioxidant potential of cells (Burak Ç imen et al, 2003).…”

Carcinomas of the renal pelvis associated with smoking and phenacetin abuse:p53 mutations and polymorphism of carcinogen-metabolising enzymes

“…In Australia, the most common risk factors are tobacco and phenacetin-containing analgesics, the latter being a stronger risk factor for the renal pelvis than for the bladder (McCredie et al, 1993). Hitherto, experimental (Nakanishi et al, 1978;Anderstrom et al, 1983) and clinical (Johansson and Wahlqvist, 1977) results have not determined whether the carcinogenic role of phenacetin in the urinary tract is through mutagenicity (Camus et al, 1982;De Flora et al, 1985;Oldham et al, 1986), stimulation of urothelial cell proliferation (Anderstrom et al, 1983;Nakanishi et al, 1978) or contribution to the causation of renal papillary necrosis, a disorder associated with infection and chronic inflammation in the upper urinary tract (McCredie et al, 1986).…”