title: Edible oil adulterants, argemone oil and butter yellow, as aetiological factors for gall bladder cancer.
abstract: 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 aetiological factors of gall bladder carcinoma (GBC) in the Indo-Gangetic basin. Twice weekly intraperitoneal (ip) administration of AO (5 ml/kg body wt) and BY (25 mg/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 6 months in female mice showed symptoms related to cachexia, jaundice and anaemia. High levels of total cholesterol, low density lipoprotein (LDL), TG, bilirubin and low level of high density lipoprotein (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 cyclooxygenase (COX-2) overexpression was found to be related to prostaglandin E2 (PGE2) production in AO treated mice but not in BY exposed animals, thereby indicating a differential pathway specific carcinogenicity. PGE2 stimulates the secretion of secreted mucins (MUC5AC), which is involved in stone formation following AO exposure. Enhanced secretion of membrane bound mucins (MUC4) in BY and AO exposed mice resulted in the activation of ErbB2 and downstream signalling 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 the AO exposed animals.
authors.affiliation: Food, Drug and Chemical Toxicology Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Post Box #80, Lucknow 226 001, India.
authors.forename: Vivek
authors.initials: V
authors.lastname: Mishra
authors.forename: Manjari
authors.initials: M
authors.lastname: Mishra
authors.forename: Kausar M
authors.initials: KM
authors.lastname: Ansari
authors.forename: Bhushan P
authors.initials: BP
authors.lastname: Chaudhari
authors.forename: Raj
authors.initials: R
authors.lastname: Khanna
authors.forename: Mukul
authors.initials: M
authors.lastname: Das
mesh_terms: D000818:Animals; D001835:Body Weight; D002273:Carcinogens / Q000633:toxicity*; D002769:Cholelithiasis / Q000209:etiology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004032:Diet; D005260:Female; D005706:Gallbladder Neoplasms / Q000209:etiology*; D008297:Male; D051379:Mice; D009077:Mucins / Q000378:metabolism; D009929:Organ Size; D010938:Plant Oils / Q000633:toxicity*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D004124:p-Dimethylaminoazobenzene / Q000633:toxicity*
chemical_list: D002273:Carcinogens; D051546:Cyclooxygenase 2; D009077:Mucins; D010938:Plant Oils; D018719:Erb-b2 Receptor Tyrosine Kinases; D004124:p-Dimethylaminoazobenzene; C030610:argemone oil; C496540:PTGS2 protein, human; C524056:Erbb2 protein, mouse