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Bisphenol S Exposure May Increase the Risk of Breast Cancer

This industrial material, widely used in paper products and plastic containers to replace BPA, has been linked with the growth and deterioration of breast tumours in mice.

Since the 1950s, the industrial chemical bisphenol A (BPA) has been widely used to create plastics and resins to produce various products, ranging from baby bottles and food and beverage containers to thermal paper for printing receipts. However, in the last decade, studies found that exposure to BPA is linked to the increased risk of breast cancer, metabolic diseases, and the disruption of the human endocrine system. Given the hazards of BPA, scientists sought to develop safer BPA substitutes, one of which is bisphenol S (BPS). Unfortunately, BPS has been shown to be an endocrine disruptor with comparable health risks to that of BPA, albeit its effects on tumour progression and metabolic processes remain unknown.

Hoping to close this knowledge gap, a team of researchers led by Professor Cai Zongwei, Chair Professor of the Department of Chemistry and Director of the State Key Laboratory of Environmental and Biological Analysis at Hong Kong Baptist University, has conducted a series of experiments to determine how exactly BPS exposure, at environmentally relevant levels, affects the development of breast tumours. Leveraging mass spectrometry imaging technology, the scientists also determined how a tumour’s morphological features and lipid and protein distribution change in response to BPS exposure.

In the study, Cai and colleagues fed three groups of mice models that had been transplanted with human breast cancer cells with different doses of BPS. The first group of mice was fed with 10 micrograms of BPS per kilogram of body weight for eight weeks daily (BPS-10 group). The second group was fed with a higher dose of 100 micrograms of BPS per kilogram of body weight (BPS-100 group), whereas the last group was served with olive oil to act as the control group.

After the eight-week experiment, the team examined tumour proliferation in the mice using morphological analysis. Their analyses revealed that the average volume and weight of the tumours in the BPS-10 group were 13 and 11 times greater than the control group respectively, while the average volume and weight of the tumours in the BPS-100 group were 4 and 4.5 times higher than that of the control. This suggests that exposure to BPS is highly associated with both the proliferation and deterioration of breast tumours.

In addition, the researchers analysed the necrotic and neoplastic regions of the breast tumours in the three mice groups since both regions share the common pathological features of solid tumours. An increase in the proportion of the necrotic region signifies tumour proliferation, while an extended neoplastic region signals the deterioration of the tumour.

According to their results, both the necrotic and neoplastic regions of the control mice remained stable, indicating that the tumours of the control mice neither proliferated nor deteriorated. However, in both the BS-10 group and the BS-100 group, there was not only an increase in tumour size but also changes in the arrangement and distribution of tumour cells that support tumour proliferation and deterioration. The necrotic regions in the BPS-10 and the BPS-100 group make up 54.7 per cent and 11.5 per cent of the average section area of the tumours respectively. This demonstrates that a low BPS dosage promotes faster tumour growth while a high BPS dosage could ultimately lead to the deterioration of the tumour.

Furthermore, the researchers detected six lipid biomarkers that regulate tumour growth by analysing the tumour tissues’ morphological characteristics and using mass spectrometry imaging. In both BPS-exposed groups, the lipids were found to be highly abundant in the necrotic regions of the breast cancers when compared with the control group. This suggests that BPS exposure may interrupt the metabolism of these tumour-regulating lipids in breast cancer tumours. Besides, twelve protein biomarkers, including those that are associated with breast tumour proliferation and deterioration, were also detected in the BPS-exposed group.

To validate their findings in humans, the research team then compared the distribution of lipids and proteins in the BPS-exposed mice with those in human breast cancer tissues and discovered similar patterns. With these findings, the team concluded that BPS can increase the risk of breast cancer in humans.

“BPA was replaced by the less studied chemical BPS in industrial production. Our research findings show that BPS may potentially be associated with breast tumour proliferation, and further study is deemed necessary to unveil more about the chemical’s possible negative impact on human health. In the long run, [the] industry may need to identify safer substitutes for both BPA and BPS. Policymakers should also establish relevant safety standards and regulations for the use of BPS,” said Professor Cai. [APBN]

Source: Zhao et al. (2021). Breast cancer proliferation and deterioration-associated metabolic heterogeneity changes induced by exposure of bisphenol S, a widespread replacement of bisphenol A. Journal of Hazardous Materials, 414, 125391.