Many medicines, carcinogens and environmental contaminants accumulate in milk — a potential health risk for breast-fed infants and those fond of dairy food. Jonker and colleagues have identified the transporter responsible for the secretion of several drugs and toxins into milk in mice, cows and humans.

The authors were studying the breast cancer resistance protein ABCG2 (also known as BCRP), an ATP-binding cassette drug transporter. This transporter expels drugs, carcinogens and environmental toxins across the cell membrane, which can lead to multidrug resistance in cancer cells. Its substrates are many and varied, including the potent dietary mutagen PhIP (2-amino-1-methyl-6-phenylimidazol[4,5-b]pyridine); topotecan, a cancer drug; cimetidine, a common treatment for ulcers and heartburn; and acyclovir, an antiviral drug.

The presence of ABCG2 in the epithelia of the intestine, kidney and bile canal indicates that this transporter helps to limit toxins in the body, getting rid of them through several excretion routes. But Jonker and colleagues found the mouse ABCG2 protein at high levels in the mammary epithelia during pregnancy and lactation. By contrast, virgin or non-lactating mice had little ABCG2 in the mammary epithelia. There is a similar pattern in cows and humans, with ABCG2 being highly expressed in lactating mammary glands, but absent from non-lactating ones.

To test whether this transporter might be responsible for the secretion of toxic compounds into milk, the researchers injected lactating wild-type and Abcg2-null mice with PhIP or topotecan. In the wild-type mice, both compounds were concentrated into the milk, unlike the knockout mice, where there was no secretion of either compound. Moreover, giving the ABCG2 inhibitor GF120918 to the wild-type mice also blocked secretion of topotecan into their milk.

Why a transporter that usually has a protective role, eliminating harmful compounds from the body, also secretes toxins to a suckling infant is hard to understand. That the presence of ABCG2 in the mammary gland has been conserved from mice to cows and humans implies an important role, and the authors speculate that the transporter might also secrete nutrients into milk, compensating for the risk from toxin contamination. They note, however, that the suckling pups of Abcg2-null mothers did not seem to be malnourished.

The findings have several useful implications. ABCG2 substrates might well accumulate in milk and their use should probably be restricted for breast-feeding mothers, and possibly for dairy cattle. Conversely, there might be cases where the transfer of drugs through milk is desirable. For instance, acyclovir, an antiviral used to treat opportunistic viral infections in HIV-positive individuals, is also an ABCG2 substrate that is concentrated in milk, and using this delivery route might reduce transmission of viruses from mother to baby.