Elucidation of dibenzo[a,l]pyrene and its metabolites as a mammary carcinogen: A comprehensive review

The general mechanism of cancer includes the metabolism of carcinogens to highly electrophilic metabolites capable of binding to DNA and other macromolecules, thereby initiating the cells. As the carcinogenesis mechanism is quite complex where diverse cellular mechanism(s) are involved in cancer promotion and progression, it is challenging to elucidate various underlying mechanisms. The intense research to study the diverse nature of cancer initiation and development with the associated risk factors and modulators has resulted in innumerable molecular and cellular markers specific to different cancer types. Almost all the exogenous compounds entering the cells are metabolized by enzymes of phase I and phase II. During biotransformation of any pro-carcinogens and other xenobiotics, the activation of phase I and suppression of phase II enzymes are required to exert their mutagenic, toxic, or carcinogenic effect. Metabolic activation, detoxification, cellular proliferation, programmed cell death, angiogenesis, and metastasis have been involved in target-specific pathways leading to oncogenic mechanisms elucidation. The interaction of parent xenobiotics with a particular target can either positively, negatively, or neutrally influence their respective cellular pathways. In the study, biotransformation by CYP450 isozymes, detoxification by GST (glutathione S-transferase) and NAT (N-acetyltransferase) isozymes, DNA adduction formation, and (dibenzo[a,l]pyrene) DBP-mediated cell proliferation have been comprehensively reviewed.