CYP4B1, a mammalian cytochrome P450 monooxygenase, belongs to the CYP4 enzyme family. It can bioactivate a variety of xenobiotics like 4-ipomeanol, leading to tissue-specific toxicities. Similar to other CYP4 family members, it has the ability to hydroxylate fatty acids and fatty alcohols. It is mainly expressed extra-hepaticly, especially in the lung, and thus does not play a major role in hepatic P450-catalyzed phase I drug metabolism. Association of its expression patterns with various cancers has been reported [1,2,3].

In experimental animals, CYP4B1 has shown roles in mutagenic activation of procarcinogens in bladders. In human bladders, CYP4B1 was detected and bladder-tumor patients had a significantly higher expression of it than non-bladder-tumor patients, suggesting it may increase the risk of bladder tumor by activating carcinogenic aromatic amines [6]. In rat lung, CYP4B1 is crucial for the bioactivation of 4-ipomeanol, as inhibition of its activity decreased the ability of lung microsomes to N-hydroxylate 2-aminofluorene and prevented lung damage from ipomeanol [7]. In addition, missense variants in CYP4B1 have been associated with an increased risk of lung cancer among the Chinese Han population, and CYP4B1 SNPs were associated with breast cancer risk in Chinese women [4,5].

In conclusion, CYP4B1 is involved in both xenobiotic and endobiotic metabolism. Its abnormal expression or genetic variants are associated with an increased risk of several cancers, such as bladder, lung, and breast cancers. Understanding CYP4B1's functions through in vivo studies can provide insights into the mechanisms of these diseases and may offer potential therapeutic strategies.