In Korea, the Asian honey bee (Apis cerana) and the European honey bee (Apis mellifera) (Hymenoptera: Apidae) are the two most common honey bee species. These two closely related species are known to have different sensitivity levels to various insecticides due to millennia of exposure to different pests and pesticides. It is reported that A. cerana is known to be more sensitive to several insecticides, such as amitraz, fenitrothion, and fipronil, than A. melllifera. Multiple studies investigated toxicological responses and related CYPome in A. mellifera, but little is known in A. cerana. The goal of this study is to elucidate the underlying mechanism of different toxicological responses between two bee species, with an emphasis on cytochrome P450 (P450), a significant enzyme involved in metabolic activities. The differences in basal P450 expression patterns were investigated by comparing the relative expression levels of P450 orthologs in several dissected organisms of each species. To compare the sensitivity against major insecticides, lethal doses of major insecticides relevant to both honey bee species were assessed by topical and oral ingestion bioassays. The determined sublethal doses of insecticides were applied to honey bees, and the inducibility of P450s was investigated by comparing the expression patterns of multiple P450s. From these results, this study eventually attempts to compare the toxicological differences between two Apis species with differences in induced cytochrome P450 expression levels.

The Varroa mite, Varroa destructor, a parasitic mite that afflicts honey bees, has become increasingly resistant to acaricides like fluvalinate due to its widespread use. The target site insensitivity mechanism, mediated by the L925V/M/I mutations in the voltage-gated sodium channel, plays a major role in resistance. Additionally, cytochrome P450 monooxygenases (Cyp450s) appear to function as a metabolic resistance factor; however, no Cyp450-mediated resistance mechanism has been reported to date. The aim of this study was to identify and characterize Cyp450s associated with fluvalinate resistance. A synergistic bioassay confirmed the involvement of Cyp450s in conferring tolerance or resistance to fluvalinate. Correlation analysis between mortality data and the expression levels of Cyp450 genes led to the identification of several candidates that may play a crucial role in fluvalinate resistance. Analysis of tissue distribution patterns revealed that these genes were most abundantly expressed in the cuticle and synganglion. This suggests that, despite their relatively low expression level, they may play a critical role in protecting the target site from fluvalinate due to its predominant expression in neuronal tissues. Functional analysis, in conjunction with baculovirus expression, demonstrated that fluvalinate has high inhibition rates against the recombinant candidate Cyp450s, suggestive of their strong interaction with fluvalinate. We discussed the potential utilization of their expression levels as a molecular marker for diagnosing metabolic resistance in field-collected Varroa mites.

1,2-Dichlorobenzene (1,2-DCB) is in various industries as solvents in herbicides, pesticides, and wax, and as degreasers or in the production of dyes. Studies on the hazards and risks of 1,2-DCB showed that this substance can cause skin corrosion, skin irritability, respiratory irritability, and certain target organ toxicity. Industrial workers are exposed to 1,2-DCB by inhalation or skin exposure and there is a lack of information on human hazards even though they can be exposed to organic compounds such as benzene or other DCB complexes rather than a single substance. In this study, we investigated the specific organ toxicity of 1,2- DCB and sex differences using whole-body inhalation in laboratory mice. Male and female mice were exposed to 0–120 ppm of the test substance for 13 weeks. After euthanization, the organs were collected, histopathological assessments and immunohistochemistry (IHC) were performed, and lipid peroxidation was analyzed. Macro and microscopic lesions were observed in the livers of male mice exposed to the test substance, and microscopic alterations were observed in the nasal cavities of male and female mice. IHC analysis of the liver confirmed a greater increase in cytochrome P450 induction in males than in female mice, and malondialdehyde and 4-hydroxynonenal were increased in both sexes by 1,2-DCB inhalation. Based on the relevant literature and experimental results, 1,2-DCB is believed to cause specific organ toxicity in the livers of male mice and the nasal cavities of both sexes of mice, which is supposed to be related to sex differences in cytochrome P450 induction and changes in lipid and oxidative products associated with the early metabolites of the test substance.