Understanding the Bhas 42 cell transformation assay: A first step in detecting carcinogenesis

When a new chemical product is formulated, it must undergo rigorous toxicology evaluations to determine that it meets regulatory compliance and public safety standards before receiving market approval. A product’s potential for carcinogenicity – the probability of causing cancer – is one of many important toxicological considerations that determine the likelihood of a product’s regulatory approval. Addressing potential for carcinogenicity, however, can be a lengthy and expensive process. Traditional methods of evaluating carcinogenicity involve in vivo studies that can take anywhere from several months to two years to complete. Responding to a need to provide testing solutions that may help reduce timelines, costs and complexities for our drug development partners, Labcorp is pleased to now offer the Bhas 42 cell transformation assay (CTA) in support of preclinical toxicology studies.

What is the CTA?

The CTA is an in vitro testing method “that aims to predict the carcinogenic potential of chemicals,” explains Darren Kidd, PhD, study director and senior scientist of in vitro alternatives and genetic toxicology for Labcorp.

The assay models a chronic exposure by treating the cells with test chemicals three times over a period of ten days. After the allotted time has passed, the cells are given a seven-day “recovery period” where the test chemical is removed and the cells are observed for signs of transformation. According to technical specialist Daniel Bramham: “The cell plates are scored for the presence of transformed colonies which are defined by six characteristics: morphological changes, deep basophilic staining, random orientation of cells, dense multi-layering, amounts of cells in a particular focal point and invasiveness into the surrounding monolayer. Taken together, these observations are indicative of cancerous transformation.”

What are the benefits of this assay?

A major advantage of the CTA is the speed with which it can deliver data. With the ability to produce results within a matter of weeks, the CTA provides answers quickly and efficiently. When used as part of a testing strategy in combination with other information such as genotoxicity data, structural-activity analysis and pharmaco- and toxicokinetic information, the CTA is an ideal first step in detecting carcinogenesis.

“The standard in vivo test can take up to two years,” Kidd says. “You’d kick yourself for not doing the CTA test first. It’s quick, inexpensive and gives a good heads-up of what’s going to happen in your long-term study.”

In addition to increasing cost efficiency, Bramham adds that the assay offers a sustainable approach to testing. “It is far less resource-intensive compared to in vivo studies,” he says. “It conserves resources both in consumables in the lab and staffing hours.”

Finally, the CTA offers the capability for high-throughput screening of chemicals, enabling simultaneous testing of a large quantity of chemicals, which can further speed up the process of identifying potential carcinogens. This is especially valuable when assessing the safety of new products, where the number of chemicals requiring testing can be very high.

The Bhas 42 CTA offers multiple benefits in detecting carcinogenesis in new chemicals, including a rapid turnaround and data that can inform decision-making and expectations ahead of longer-term studies. While not recommended as a standalone assay, the Bhas 42 CTA is ideal as part of a testing strategy in toxicology studies.