Carcinogenic potential of argemone oil (AO) and butter yellow (BY), the adulterants encountered in edible oil, in gall bladder of Swiss albino mice was undertaken to investigate the potential etiological factors of gall bladder carcinoma (GBC) in the Indo-Gangetic basin. Twice weekly intraperitoneal (ip) administration of AO (5ml/kg body wt) and BY (25mg/kg body wt) to Swiss albino male and female mice for 30 and 60 days indicated that females were more vulnerable to these adulterants in terms of responses to inflammatory markers. Subsequent experiments with dietary exposure of AO (1%) and BY (0.06%) for six months in female mice showed symptoms related to cachexia, jaundice and anemia. High levels of total cholesterol, LDL, TG, Bilirubin and low level of HDL as well as gallstone formation was shown by AO exposure only, leading to the development of adenocarcinoma. BY exposure resulted in adenoma and hyperplasia without stone formation. The COX-2 overexpression was found to be related to PGE2 production in AO treated mice but not in BY exposed animals, thereby indicating a differential pathway specific carcinogenicity. PGE2 stimulates the secretion of MUC5AC, which is involved in stone formation following AO exposure. Enhanced secretion of MUC4 in BY and AO exposed mice resulted in activation of ErbB2 and downstream signaling such as p-AKT, p-ERK and p-JNK, which ultimately affects the target proteins, p53 and p21 leading to adenoma and adenocarcinoma, respectively. The study suggests that AO and BY are responsible for producing GBC in mice along with stone formation in AO exposed animals.

Mishra et al.; European Journal of Cancer; 2012; 48; 2075-2085.